<?xml version="1.0" encoding="UTF-8"?><section ID="ID_8f305ce2-a171-4677-860a-175d8179fbe1">
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<code code="34084-4" codeSystem="2.16.840.1.113883.6.1" displayName="ADVERSE REACTIONS SECTION"/>
<title>6 ADVERSE REACTIONS</title>
<text>
<paragraph>The following adverse reactions are discussed elsewhere in the labeling:</paragraph>
<list listType="unordered">
<item>
<caption>•</caption>Myelodysplastic Syndrome/Acute Myeloid Leukemia <content styleCode="italics">[see <linkHtml href="#ID_b7487ab1-239a-42a2-8ee2-7c05498b47f6">Warnings and Precautions (5.1)</linkHtml>]</content>
</item>
<item>
<caption>•</caption>Pneumonitis <content styleCode="italics">[see <linkHtml href="#ID_be2c9632-7c6a-41ed-910a-455987801998">Warnings and Precautions (5.2)</linkHtml>]</content>
</item>
<item>
<caption>•</caption>Venous Thromboembolism <content styleCode="italics">[see </content>
<content styleCode="italics">
<linkHtml href="#ID_9d7c095f-cd4c-4495-bd4a-2ca07305f94f">Warnings and Precautions (5.3)</linkHtml>
</content>
<content styleCode="italics">]</content>
</item>
</list>
</text>
<effectiveTime value="20231106"/>
<excerpt>
<highlight>
<text>
<paragraph>Most common adverse reactions (≥10%) in clinical trials:</paragraph>
<list listType="unordered">
<item>
<caption>•</caption>as a single agent were nausea, fatigue (including asthenia), anemia, vomiting, diarrhea, decreased appetite, headache, dysgeusia, cough, neutropenia, dyspnea, dizziness, dyspepsia, leukopenia, and thrombocytopenia. <linkHtml href="#ID_27d482b2-2224-440e-ad58-0ad5772ae413">(6.1)</linkHtml>
</item>
<item>
<caption>•</caption>in combination with bevacizumab were nausea, fatigue (including asthenia), anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and headache. (<linkHtml href="#ID_27d482b2-2224-440e-ad58-0ad5772ae413">6.1</linkHtml>)</item>
<item>
<caption>•</caption>in combination with abiraterone and prednisone or prednisolone were anemia, fatigue, nausea, diarrhea, decreased appetite, lymphopenia, dizziness, and abdominal pain. (<linkHtml href="#ID_27d482b2-2224-440e-ad58-0ad5772ae413">6.1</linkHtml>)</item>
</list>
<paragraph>
<content styleCode="bold">To report SUSPECTED ADVERSE REACTIONS, contact </content>
<content styleCode="bold">AstraZeneca at 1-800-236-9933</content>
<content styleCode="bold"> or FDA at 1-800-FDA-1088 or <linkHtml href="http://www.fda.gov/medwatch">www.fda.gov/medwatch.</linkHtml>
</content>
</paragraph>
</text>
</highlight>
</excerpt>
<component>
<section ID="ID_27d482b2-2224-440e-ad58-0ad5772ae413">
<id root="35346b2c-7d61-4539-aa21-e05b17b35555"/>
<code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
<title>6.1 Clinical Trial Experience</title>
<text>
<paragraph>Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.</paragraph>
<paragraph>Unless otherwise specified, the data described in the WARNINGS AND PRECAUTIONS reflect exposure to Lynparza as a single agent in 2901 patients; 2135 patients with exposure to 300 mg twice daily tablet dose including five controlled, randomized, trials (SOLO-1, SOLO-2, OlympiAD, POLO, and PROfound) and to 400 mg twice daily capsule dose in 766 patients in other trials that were pooled to conduct safety analyses. In addition to the 2901 patients, certain subsections in the WARNINGS AND PRECAUTIONS include adverse reactions observed with exposure to Lynparza with abiraterone (n=398) in PROpel. All patients with metastatic castration resistant prostate cancer received concomitant ADT or previous bilateral orchiectomy. </paragraph>
<paragraph>In the pooled safety population, 56% of patients were exposed for 6 months or longer and 28% were exposed for greater than one year in the Lynparza group.</paragraph>
<paragraph>In this pooled safety population, the most common adverse reactions in ≥10% of patients were nausea (60%), fatigue (55%), anemia (36%), vomiting (32%), diarrhea (24%), decreased appetite (22%), headache (16%), dysgeusia (15%), cough (15%), neutropenia (14%), dyspnea (14%), dizziness (12%), dyspepsia (12%), leukopenia (11%), and thrombocytopenia (10%). </paragraph>
<paragraph>
<content styleCode="underline">First-Line Maintenance Treatment of <content styleCode="italics">BRCA</content>-mutated Advanced Ovarian Cancer</content>
</paragraph>
<paragraph>
<content styleCode="italics">SOLO-1</content>
</paragraph>
<paragraph>The safety of Lynparza for the maintenance treatment of patients with BRCA-mutated advanced ovarian cancer following first-line treatment with platinum-based chemotherapy was investigated in SOLO-<content styleCode="italics">1 [see <linkHtml href="#ID_1cd4967a-8800-4f31-9795-c91580895e7e">Clinical Studies (14.1)</linkHtml>]</content>. Patients received Lynparza tablets 300 mg orally twice daily (n=260) or placebo (n=130) until disease progression or unacceptable toxicity. The median duration of study treatment was 25 months for patients who received Lynparza and 14 months for patients who received placebo.</paragraph>
<paragraph>Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 52% and dose reductions due to an adverse reaction occurred in 28%. The most frequent adverse reactions leading to dose interruption or reduction of Lynparza were anemia (23%), nausea (14%), and vomiting (10%). Discontinuation due to adverse reactions occurred in 12% of patients receiving Lynparza. The most frequent adverse reactions that led to discontinuation of Lynparza were fatigue (3.1%), anemia (2.3%), and nausea (2.3%).</paragraph>
<paragraph>Tables 2 and 3 summarize adverse reactions and laboratory abnormalities in SOLO-1.</paragraph>
<table cellpadding="0pt" width="100%">
<caption>Table 2 Adverse Reactions<footnote ID="_Ref38455000">Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.</footnote> in SOLO-1 (≥10% of Patients Who Received Lynparza)</caption>
<col width="50%"/>
<col width="13%"/>
<col width="12%"/>
<col width="14%"/>
<col width="12%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Adverse Reaction</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=260</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=130</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">3 – 4 (%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All</content>
</paragraph>
<paragraph>
<content styleCode="bold">Grades<br/>(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">3 – 4 (%)</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>77</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>38</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Abdominal pain<footnote ID="_Ref38455024">Includes abdominal pain, abdominal pain lower, abdominal pain upper, abdominal distension, abdominal discomfort, and abdominal tenderness.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>45</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>40</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Diarrhea<footnote ID="_Ref38455040">Includes colitis, diarrhea, and gastroenteritis.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>37</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>26</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Constipation</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Dyspepsia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Stomatitis<footnote ID="_Ref38455058">Includes stomatitis, aphthous ulcer, and mouth ulceration.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Fatigue<footnote ID="_Ref38455073">Includes asthenia, fatigue, lethargy, and malaise.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>67</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>42</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and Lymphatic System Disorders </content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Anemia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>38</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>21</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Neutropenia<footnote ID="_Ref38455087">Includes neutropenia and febrile neutropenia.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Leukopenia<footnote ID="_Ref38455102">Includes leukopenia and white blood cell count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Thrombocytopenia<footnote ID="_Ref38455135">Includes platelet count decreased and thrombocytopenia.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Infections and Infestations</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Upper respiratory tract<br/> infection/ influenza/nasopharyngitis/bronchitis </paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> UTI<footnote ID="_Ref38455252">Includes urosepsis, urinary tract infection, urinary tract pain, and pyuria.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Nervous System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Dysgeusia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>26</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Dizziness</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Metabolism and Nutrition Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Decreased appetite</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Respiratory, Thoracic and Mediastinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph> Dyspnea<footnote ID="_Ref38455271">Includes dyspnea and dyspnea exertional.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions that occurred in <10% of patients receiving Lynparza were increased blood creatinine (8%), lymphopenia (6%), VTE (3%), hypersensitivity (2%), MDS/AML (1.9%), dermatitis (1%), and increased mean cell volume (0.4%).</paragraph>
<table width="100%">
<caption>Table 3 Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-1</caption>
<col width="50%"/>
<col width="13%"/>
<col width="13%"/>
<col width="12%"/>
<col width="12%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Laboratory </content>
</paragraph>
<paragraph>
<content styleCode="bold">Parameter</content>
<footnote ID="_Ref522754567">Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.</footnote>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnote ID="_Ref522754583">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
<content styleCode="bold">=260</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnoteRef IDREF="_Ref522754583"/>
<content styleCode="bold">=130</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in hemoglobin</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>87</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>63</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Increase in mean corpuscular volume</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>87</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>-</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>43</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>-</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in leukocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>70</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>52</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in lymphocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>67</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>29</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in absolute neutrophil count</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>51</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>38</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in platelets</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>Increase in serum creatinine</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>34</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="underline">First-line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer in Combination with Bevacizumab</content>
</paragraph>
<paragraph>
<content styleCode="italics">PAOLA-1</content>
</paragraph>
<paragraph>The safety of Lynparza in combination with bevacizumab for the maintenance treatment of patients with advanced ovarian cancer following first-line treatment containing platinum-based chemotherapy and bevacizumab was investigated in PAOLA-1 <content styleCode="italics">[see </content>
<content styleCode="italics">
<linkHtml href="#ID_5a17802b-5c8c-4312-99af-7dddee79b3ea">Clinical Studies (14.2)</linkHtml>]</content>. This study was a placebo-controlled, double-blind study in which 802 patients received either Lynparza 300 mg BID in combination with bevacizumab (n=535) or placebo in combination with bevacizumab (n=267) until disease progression or unacceptable toxicity. The median duration of treatment with Lynparza was 17.3 months and 11 months for bevacizumab post-randomization on the Lynparza/bevacizumab arm.</paragraph>
<paragraph>Fatal adverse reactions occurred in 1 patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received Lynparza/bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).</paragraph>
<paragraph>Dose interruptions due to an adverse reaction of any grade occurred in 54% of patients receiving Lynparza/bevacizumab and dose reductions due to an adverse reaction occurred in 41% of patients who received Lynparza/bevacizumab.</paragraph>
<paragraph>The most frequent adverse reactions leading to dose interruption in the Lynparza/bevacizumab arm were anemia (21%), nausea (7%), vomiting (3%), and fatigue (3%), and the most frequent adverse reactions leading to reduction in the Lynparza/bevacizumab arm were anemia (19%), nausea (7%), and fatigue (4%).</paragraph>
<paragraph>Discontinuation due to adverse reactions occurred in 20% of patients receiving Lynparza/bevacizumab. Specific adverse reactions that most frequently led to discontinuation in patients treated with Lynparza/bevacizumab were anemia (4%) and nausea (3%). </paragraph>
<paragraph>The most common adverse reactions (≥ 10%) for patients receiving Lynparza/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), diarrhea (18%), neutropenia (18%), leukopenia (18%), urinary tract infection (15%), and headache (14%).</paragraph>
<paragraph>Tables 4 and 5 summarize adverse reactions and laboratory abnormalities in PAOLA-1, respectively.</paragraph>
<table width="100%">
<caption>Table 4 Adverse Reactions<footnote ID="_Ref40094079">Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.</footnote> Occurring in ≥10% of Patients Treated with Lynparza/bevacizumab in PAOLA-1 and at ≥5% Frequency Compared to the Placebo/bevacizumab Arm</caption>
<col width="39%"/>
<col width="14%"/>
<col width="14%"/>
<col width="17%"/>
<col width="16%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Adverse Reactions</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza/bevacizumab </content>
</paragraph>
<paragraph>
<content styleCode="bold">n=535</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo/bevacizumab <br/>n=267</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Fatigue (including asthenia)<footnote ID="_Ref38534392">Includes asthenia and fatigue.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>53</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>32</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1.5</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>53</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2.4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1.7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1.9</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and Lymphatic Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Anemia<footnote ID="_Ref38534400">Includes anemia, anemia macrocytic, erythropenia, haematocrit decreased, haemoglobin decreased, normochromic anemia, normochromic normocytic anemia, normocytic anemia, and red blood cell count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>41</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.4</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Lymphopenia<footnote ID="_Ref66440937">Includes B-lymphocyte count decreased, lymphocyte count decreased, lymphopenia, and T-lymphocyte count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>24</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1.1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph> Leukopenia<footnote ID="_Ref38534415">Includes leukopenia and white blood cell count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>1.9</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>1.5</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions that occurred in <10% of patients receiving Lynparza/bevacizumab were dysgeusia (8%), dyspnea (8%), stomatitis (5%), dyspepsia (4.3%), erythema (3%), dizziness (2.6%), hypersensitivity (1.7%), and MDS/AML (0.7%).</paragraph>
<paragraph>Venous thromboembolism occurred more commonly in patients receiving Lynparza/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).</paragraph>
<table width="100%">
<caption>Table 5 Laboratory Abnormalities Reported in ≥25% of Patients in PAOLA-1<footnote ID="_Ref40095548">Reported within 30 days of the last dose.</footnote>
</caption>
<col width="47%"/>
<col width="15%"/>
<col width="13%"/>
<col width="13%"/>
<col width="12%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Laboratory Parameter</content>
<footnote ID="_Ref40095697">Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.</footnote>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza/bevacizumab <br/>n</content>
<footnoteRef IDREF="_Ref40095697"/>
<content styleCode="bold">=535</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo/bevacizumab <br/>n</content>
<footnote ID="_Ref23949789">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
<content styleCode="bold">=267</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in hemoglobin</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>79</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>55</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.4</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in lymphocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>63</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>42</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3.0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Increase in serum creatinine</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>61</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>36</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.4</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in leukocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>59</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3.4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>45</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2.2</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in absolute neutrophil count</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3.7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>Decrease in platelets</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>2.4</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0.4</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="underline">Maintenance Treatment of <content styleCode="italics">BRCA</content>-mutated Recurrent Ovarian Cancer</content>
</paragraph>
<paragraph>
<content styleCode="italics">SOLO-2</content>
</paragraph>
<paragraph>The safety of Lynparza for the maintenance treatment of patients with platinum sensitive g<content styleCode="italics">BRCA</content>m ovarian cancer was investigated in SOLO-2 <content styleCode="italics">[see </content>
<content styleCode="italics">
<linkHtml href="#ID_B383168C-2AFC-46A7-B1EC-09E1D4930470">Clinical Studies (14.3)</linkHtml>]</content>. Patients received Lynparza tablets 300 mg orally twice daily (n=195) or placebo (n=99) until disease progression or unacceptable toxicity. The median duration of study treatment was 19.4 months for patients who received Lynparza and 5.6 months for patients who received placebo. </paragraph>
<paragraph>Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 45% and dose reductions due to an adverse reaction occurred in 27%. The most frequent adverse reactions leading to dose interruption or reduction of Lynparza were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%). Discontinuation due to an adverse reaction occurred in 11% of patients receiving Lynparza.</paragraph>
<paragraph>Tables 6 and 7 summarize adverse reactions and laboratory abnormalities in SOLO-2.</paragraph>
<table width="100%">
<caption>Table 6 Adverse Reactions<footnote ID="_Ref40196145">Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.</footnote> in SOLO-2 (≥20% of Patients Who Received Lynparza)</caption>
<col width="47%"/>
<col width="14%"/>
<col width="13%"/>
<col width="13%"/>
<col width="13%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Adverse Reaction</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=195</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=99</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>76</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>33</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>37</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>33</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Stomatitis<footnote ID="_Ref40196200">Represents grouped term consisting of abscess oral, aphthous ulcer, gingival abscess, gingival disorder, gingival pain, gingivitis, mouth ulceration, mucosal infection, mucosal inflammation, oral candidiasis, oral discomfort, oral herpes, oral infection, oral mucosal erythema, oral pain, oropharyngeal discomfort, and oropharyngeal pain.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Fatigue including asthenia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>66</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>39</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and Lymphatic Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Anemia<footnote ID="_Ref40196219">Represents grouped term consisting of anemia, hematocrit decreased, hemoglobin decreased, iron deficiency, mean cell volume increased, and red blood cell count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>44</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Infections and Infestations</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Nasopharyngitis/URI/sinusitis/ rhinitis/influenza</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>36</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>29</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Musculoskeletal and Connective Tissue Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Arthralgia/myalgia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Nervous System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Dysgeusia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Headache</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>26</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Metabolism and Nutrition Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph> Decreased appetite</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions that occurred in <20% of patients receiving Lynparza were neutropenia (19%), cough (18%), leukopenia (16%), hypomagnesemia (14%), thrombocytopenia (14%), dizziness (13%), dyspepsia (11%), increased creatinine (11%), MDS/AML (8%), edema (8%), rash (6%), VTE (5%), and lymphopenia (1%).</paragraph>
<table width="100%">
<caption>Table 7 Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-2</caption>
<col width="33%"/>
<col width="17%"/>
<col width="17%"/>
<col width="16%"/>
<col width="17%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Laboratory Parameter</content>
<footnote ID="_Ref96937793">Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.</footnote>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnote ID="_Ref23950038">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
<content styleCode="bold">=195 </content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnoteRef IDREF="_Ref23950038"/>
<content styleCode="bold">=99</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Increase in mean corpuscular volume<footnote ID="_Ref23950055">Represents the proportion of subjects whose mean corpuscular volume was > upper limit of normal (ULN).</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>89</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>-</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>52</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>-</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in hemoglobin</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>83</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>69</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in leukocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>69</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>48</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in lymphocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>67</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>37</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in absolute neutrophil count</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>51</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>34</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Increase in serum creatinine</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>44</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>29</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>Decrease in platelets</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>42</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="underline">Adjuvant Treatment of germline <content styleCode="italics">BRCA</content>-mutated HER2-negative High Risk Early Breast Cancer</content>
</paragraph>
<paragraph>
<content styleCode="italics">
<content styleCode="underline">OlympiA</content>
</content>
</paragraph>
<paragraph>The safety of Lynparza as monotherapy for the adjuvant treatment of patients with gBRCA-mutated HER2-negative high risk early breast cancer was investigated in OlympiA <content styleCode="italics">[see </content>
<content styleCode="italics">
<linkHtml href="#ID_1f0da7ec-7655-4d5f-848c-0d023fa69387">Clinical Studies (14.4)</linkHtml>
</content>
<content styleCode="italics">]</content>. This study was a randomized, double-blind, multi-center study in which patients received either Lynparza tablets 300 mg orally twice daily (n=911) or placebo (n=904) for a total of 1 year, or until disease recurrence, or unacceptable toxicity. The median duration of treatment was 1 year in both arms.</paragraph>
<paragraph>Dose interruptions due to an adverse reaction of any grade occurred in 31% of patients receiving Lynparza; dose reductions due to an adverse reaction occurred in 23% of patients receiving Lynparza. The most frequent adverse reactions leading to dose interruption of Lynparza were anemia (11%), neutropenia (6%), nausea (5%), leukopenia (3.5%), fatigue (3%), and vomiting (2.9%) and the most frequent adverse reactions leading to dose reduction of Lynparza were anemia (8%), nausea (4.7%), neutropenia (4.2%), fatigue (3.3%), leukopenia (1.8%), and vomiting (1.5%). Discontinuation due to adverse reactions occurred in 10% of patients receiving Lynparza. The adverse reactions that most frequently led to discontinuation of Lynparza were nausea (2%), anemia (1.8%), and fatigue (1.3%).</paragraph>
<paragraph>Tables 8 and 9 summarize the adverse reactions and laboratory abnormalities, respectively, in patients in OlympiA.</paragraph>
<table width="100%">
<caption>Table 8 Adverse Reactions<footnote ID="_Ref82172317">Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03</footnote> in OlympiA (≥ 10% of Patients Who Received Lynparza)</caption>
<col width="35%"/>
<col width="15%"/>
<col width="17%"/>
<col width="16%"/>
<col width="16%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>
<content styleCode="bold">Adverse Reactions</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=911</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>
<content styleCode="bold">Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=904</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>57</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Stomatitis<footnote ID="_Ref82172462">Includes aphthous ulcer, mouth ulceration, and stomatitis.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>4.5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
<td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/>
<td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/>
<td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/>
<td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Fatigue (including asthenia)</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>42</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>1.8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.7</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and Lymphatic Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Anemia<footnote ID="_Ref82172560">Includes anemia, anemia macrocytic, erythropenia, hematocrit decreased, hemoglobin decreased, normochromic anemia, normochromic normocytic anemia, normocytic anemia, and red blood cell count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>24</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>3.9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Leukopenia<footnote ID="_Ref82172575">Includes leukopenia and white blood cell count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Neutropenia<footnote ID="_Ref82172583">Includes agranulocytosis, febrile neutropenia, granulocyte count decreased, granulocytopenia, idiopathic neutropenia, neutropenia, neutropenic infection, neutropenic sepsis, and neutrophil count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.8</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Nervous System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Headache</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Dysgeusia<footnote ID="_Ref82599506">Includes dysgeusia and taste disorder.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>4.8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Dizziness</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.1</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Metabolism and Nutrition Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph> Decreased appetite </paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>0.2</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions that occurred in <10% of patients receiving Lynparza were cough (9.2%), lymphopenia (7%), dyspepsia (6%), upper abdominal pain (4.9%), rash (4.9%), dyspnea (4.2%), thrombocytopenia (4.2%), increase in creatinine (2%), hypersensitivity (0.9%), VTE (0.5%), dermatitis (0.5%), increase in mean corpuscular volume (0.2%), and MDS/AML (0.2%).</paragraph>
<table width="100%">
<caption>Table 9 Laboratory Abnormalities Reported in ≥25% of Patients in OlympiA</caption>
<col width="25%"/>
<col width="19%"/>
<col width="17%"/>
<col width="20%"/>
<col width="19%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>
<content styleCode="bold">Laboratory Parameter</content>
<footnote ID="_Ref82695073">Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.</footnote>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnote ID="_Ref82174437">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
<content styleCode="bold">= 911</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>
<content styleCode="bold">Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnoteRef IDREF="_Ref82174437"/>
<content styleCode="bold">=904</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>Decrease in lymphocytes </paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>77</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>59</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>3.7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>Increase in mean corpuscular volume<footnote ID="_Ref82599569">Represents the proportion of subjects whose mean corpuscular volume was > ULN.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>67</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>4.8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>Decrease in hemoglobin </paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>65</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>31</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.9</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>Decrease in leukocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>64</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>42</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>0.7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>Decrease in absolute neutrophil count</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>39</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>1.1</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="underline">
<content styleCode="italics">Germline BRCA</content>-mutated HER2-negative Metastatic Breast Cancer </content>
</paragraph>
<paragraph>
<content styleCode="italics">
<content styleCode="underline">OlympiAD</content>
</content>
</paragraph>
<paragraph>The safety of Lynparza was evaluated in g<content styleCode="italics">BRCA</content>m patients with HER2-negative metastatic breast cancer who had previously received up to two lines of chemotherapy for the treatment of metastatic disease in OlympiAD <content styleCode="italics">[see </content>
<content styleCode="italics">
<linkHtml href="#ID_7EFF5AF5-AD29-4F8E-A7CC-19D136EE42EA">Clinical Studies (14.5)</linkHtml>
</content>
<content styleCode="italics">]</content>. Patients received either Lynparza tablets 300 mg orally twice daily (n=205) or a chemotherapy (capecitabine, eribulin, or vinorelbine) of the healthcare provider’s choice (n=91) until disease progression or unacceptable toxicity. The median duration of study treatment was 8.2 months in patients who received Lynparza and 3.4 months in patients who received chemotherapy. </paragraph>
<paragraph>Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 35% and dose reductions due to an adverse reaction occurred in 25%. Discontinuation due to an adverse reaction occurred in 5% of patients receiving Lynparza. </paragraph>
<paragraph>Tables 10 and 11 summarize the adverse reactions and laboratory abnormalities in OlympiAD.</paragraph>
<table width="100%">
<caption>Table 10 Adverse Reactions<footnote ID="_Ref37254486">Graded according to NCI CTCAE v4.0.</footnote> in OlympiAD (≥20% of Patients Who Received Lynparza)</caption>
<col width="39%"/>
<col width="14%"/>
<col width="14%"/>
<col width="17%"/>
<col width="16%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Adverse Reaction</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=205</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Chemotherapy</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=91</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>58</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>21</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and Lymphatic Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Anemia<footnote ID="_Ref37254509">Represents grouped terms consisting of anemia (anemia erythropenia, hematocrit decreased, hemoglobin decreased, and red blood cell count decreased).</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>40</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>26</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Neutropenia<footnote ID="_Ref37254562">Represents grouped terms consisting of neutropenia (febrile neutropenia, granulocyte count decreased, granulocytopenia, neutropenia, neutropenic infection, neutropenic sepsis, and neutrophil count decreased).</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>50</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>26</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Leukopenia<footnote ID="_Ref40362619">Represents grouped terms consisting of leukopenia (leukopenia and white blood cell count decreased).</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>25</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>31</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Fatigue (including asthenia)</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>37</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>36</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>
<content styleCode="bold">Infections and Infestations</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Respiratory tract infection<footnote ID="_Ref37254577">Represents grouped terms consisting of bronchitis, influenza, lower respiratory tract infection, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Nervous System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph> Headache</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions that occurred in <20% of patients receiving Lynparza were cough (18%), decreased appetite (16%), thrombocytopenia (11%), dysgeusia (9%), lymphopenia (8%), dyspepsia (8%), dizziness (7%), stomatitis (7%), upper abdominal pain (7%), rash (5%), increase in serum creatinine (3%), dermatitis (1%), and VTE (1%). </paragraph>
<table width="100%">
<caption>Table 11 Laboratory Abnormalities Reported in ≥25% of Patients in OlympiAD</caption>
<col width="39%"/>
<col width="14%"/>
<col width="17%"/>
<col width="17%"/>
<col width="14%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>
<content styleCode="bold">Laboratory Parameter</content>
<footnote ID="_Ref37254723">Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.</footnote>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnote ID="_Ref37254748">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
<content styleCode="bold">= 205</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Chemotherapy</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnoteRef IDREF="_Ref37254748"/>
<content styleCode="bold">= 91</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in hemoglobin</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>82</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>66</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in lymphocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>73</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>21</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>63</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in leukocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>71</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>70</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Increase in mean corpuscular volume<footnote ID="_Ref37254809">Represents the proportion of subjects whose mean corpuscular volume was > ULN.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>71</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>-</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>33</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>-</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in absolute neutrophil count</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>46</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>65</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>38</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>Decrease in platelets</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>33</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="underline">First-line Maintenance Treatment of Germline <content styleCode="italics">BRCA</content>-mutated Metastatic Pancreatic Adenocarcinoma</content>
</paragraph>
<paragraph>
<content styleCode="italics">POLO</content>
</paragraph>
<paragraph>The safety of Lynparza as maintenance treatment of germline <content styleCode="italics">BRCA</content>-mutated metastatic pancreatic adenocarcinoma following first-line treatment with platinum-based chemotherapy was evaluated in POLO <content styleCode="italics">[see </content>
<content styleCode="italics">
<linkHtml href="#ID_a1d1299e-3abe-4f12-a454-2eda60a57f56">Clinical Studies (14.6)</linkHtml>
</content>
<content styleCode="italics">]</content>. Patients received Lynparza tablets 300 mg orally twice daily (n=90) or placebo (n=61) until disease progression or unacceptable toxicity. Among patients receiving Lynparza, 34% were exposed for 6 months or longer and 25% were exposed for greater than one year.</paragraph>
<paragraph>Among patients who received Lynparza, dosage interruptions due to an adverse reaction of any grade occurred in 35% and dosage reductions due to an adverse reaction occurred in 17%. The most frequent adverse reactions leading to dosage interruption or reduction in patients who received Lynparza were anemia (11%), vomiting (5%), abdominal pain (4%), asthenia (3%), and fatigue (2%). Discontinuation due to adverse reactions occurred in 6% of patients receiving Lynparza. The most frequent adverse reaction that led to discontinuation of Lynparza was fatigue (2.2%).</paragraph>
<paragraph>Tables 12 and 13 summarize the adverse reactions and laboratory abnormalities in patients in POLO.</paragraph>
<table cellpadding="0pt" width="100%">
<caption>Table 12 Adverse Reactions<footnote ID="_Ref37767241">Graded according to NCI CTCAE, version 4.0.</footnote> in POLO (Occurring in ≥10% of Patients who Received Lynparza)</caption>
<col width="46%"/>
<col width="13%"/>
<col width="15%"/>
<col width="12%"/>
<col width="14%"/>
<thead>
<tr>
<th align="center" rowspan="2" styleCode="Rrule Lrule Toprule " valign="top">
<content styleCode="bold">Adverse Reaction</content>
</th>
<th align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">Lynparza tablets</content>
<br/>
<content styleCode="bold">(n=91)</content>
<footnote ID="_Ref37767491">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
</th>
<th align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">Placebo</content>
<br/>
<content styleCode="bold">(n=60)</content>
<footnoteRef IDREF="_Ref37767491"/>
</th>
</tr>
<tr>
<th align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<content styleCode="bold">All Grades (%)</content>
</th>
<th align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<content styleCode="bold">Grades</content>
<br/>
<content styleCode="bold">3 – 4 (%)</content>
</th>
<th align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<content styleCode="bold">All</content>
<br/>
<content styleCode="bold">Grades</content>
<br/>
<content styleCode="bold"> (%)</content>
</th>
<th align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<content styleCode="bold">Grades</content>
<br/>
<content styleCode="bold">3 – 4 (%)</content>
</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="3" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top"/>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top"/>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Fatigue<footnote ID="_Ref37767513">Includes asthenia and fatigue.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>60</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>45</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Abdominal pain<footnote ID="_Ref37767543">Includes abdominal pain, abdominal pain upper, and abdominal pain lower.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>34</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>37</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>29</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Constipation</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Stomatitis<footnote ID="_Ref37767564">Includes stomatitis and mouth ulceration.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and Lymphatic System Disorders </content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Anemia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Thrombocytopenia<footnote ID="_Ref37767584">Includes platelets count decreased and thrombocytopenia.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Neutropenia<footnote ID="_Ref37767576">Includes neutropenia, febrile neutropenia, and neutrophil count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Metabolism and Nutrition Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Decreased appetite</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>25</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Musculoskeletal and Connective Tissue Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Back pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Arthralgia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Skin and Subcutaneous Tissue Disorder</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Rash<footnote ID="_Ref37767675">Includes rash erythematous, rash macular, and rash maculo-papular.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Respiratory, Thoracic and Mediastinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Dyspnea<footnote ID="_Ref37767688">Includes dyspnea and dyspnea exertional.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Infections and Infestations</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph> Nasopharyngitis</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Nervous System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph> Dysgeusia</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions that occurred in <10% of patients receiving Lynparza were cough (9%), abdominal pain upper (7%), blood creatinine increased (7%), dizziness (7%), headache (7%), dyspepsia (5%), leukopenia (5%), VTE (3%), hypersensitivity (2%), and lymphopenia (2%).</paragraph>
<table width="100%">
<caption>Table 13 Laboratory Abnormalities Reported in ≥25% of Patients in POLO</caption>
<col width="46%"/>
<col width="18%"/>
<col width="12%"/>
<col width="12%"/>
<col width="12%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Laboratory</content>
</paragraph>
<paragraph>
<content styleCode="bold">Parameter</content>
<footnote ID="_Ref38535087">Patients were allowed to enter POLO with hemoglobin ≥9 g/dL (CTCAE Grade 2) and other laboratory values of CTCAE Grade 1.</footnote>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnote ID="_Ref38535114">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
<content styleCode="bold">=91</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnoteRef IDREF="_Ref38535114"/>
<content styleCode="bold">=60</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4 (%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Increase in serum creatinine</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>99</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>85</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in hemoglobin</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>86</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>65</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Increase in mean corpuscular volume<footnote ID="_Ref38535130">Represents the proportion of subjects whose mean corpuscular volume was > ULN.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>71</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>-</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>-</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in lymphocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>61</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in platelets</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>56</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>39</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in leukocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>50</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>Decrease in absolute neutrophil count</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>25</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="underline">HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer</content>
</paragraph>
<paragraph>
<content styleCode="italics">PROfound</content>
</paragraph>
<paragraph>The safety of Lynparza as monotherapy was evaluated in patients with mCRPC and HRR gene mutations who have progressed following prior treatment with enzalutamide or abiraterone in PROfound <content styleCode="italics">[see </content>
<content styleCode="italics">
<linkHtml href="#ID_d17760ea-331e-411a-8649-1791b3994867">Clinical Studies (14.7)</linkHtml>
</content>
<content styleCode="italics">]</content>. This study was a randomized, open-label, multi-center study in which 386 patients received either Lynparza tablets 300 mg orally twice daily (n=256) or investigator’s choice of enzalutamide or abiraterone acetate (n=130) until disease progression or unacceptable toxicity. Among patients receiving Lynparza, 62% were exposed for 6 months or longer and 20% were exposed for greater than one year.</paragraph>
<paragraph>Fatal adverse reactions occurred in 4% of patients treated with Lynparza. These included pneumonia (1.2%), cardiopulmonary failure (0.4%), aspiration pneumonia (0.4%), intestinal diverticulum (0.4%), septic shock (0.4%), Budd-Chiari Syndrome (0.4%), sudden death (0.4%), and acute cardiac failure (0.4%).</paragraph>
<paragraph>Serious adverse reactions occurred in 36% of patients receiving Lynparza. The most frequent serious adverse reactions (≥2%) were anemia (9%), pneumonia (4%), pulmonary embolism (2%), fatigue/asthenia (2%), and urinary tract infection (2%).</paragraph>
<paragraph>Dose interruptions due to an adverse reaction of any grade occurred in 45% of patients receiving Lynparza; dose reductions due to an adverse reaction occurred in 22% of Lynparza patients. The most frequent adverse reactions leading to dose interruption of Lynparza were anemia (25%) and thrombocytopenia (6%) and the most frequent adverse reaction leading to reduction of Lynparza was anemia (16%). Discontinuation due to adverse reactions occurred in 18% of Lynparza. The adverse reaction that most frequently led to discontinuation of Lynparza was anemia (7%).</paragraph>
<paragraph>Tables 14 and 15 summarize the adverse reactions and laboratory abnormalities, respectively, in patients in PROfound.</paragraph>
<table width="100%">
<caption>Table 14 Adverse Reactions<footnote ID="_Ref40249232">Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.</footnote> Reported in ≥10% of Patients in PROfound</caption>
<col width="35%"/>
<col width="15%"/>
<col width="17%"/>
<col width="16%"/>
<col width="16%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Adverse Reactions</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n=256</content>
</paragraph>
<paragraph>
<content styleCode="bold"> </content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Enzalutamide or abiraterone </content>
</paragraph>
<paragraph>
<content styleCode="bold">n=130</content>
</paragraph>
<paragraph>
<content styleCode="bold"> </content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and lymphatic disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Anemia<footnote ID="_Ref40249300">Includes anemia and hemoglobin decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>46</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>21</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Thrombocytopenia<footnote ID="_Ref40249329">Includes platelet count decreased and thrombocytopenia.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Gastrointestinal disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>41</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>21</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">General disorders and administration site conditions</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Fatigue (including asthenia)</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>41</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>32</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Metabolism and nutrition disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Decreased appetite </paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Respiratory, thoracic, and mediastinal disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Cough</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph> Dyspnea</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions that occurred in <10% of patients receiving Lynparza were neutropenia (9%), VTE (7%), dizziness (7%), dysgeusia (7%), dyspepsia (7%), headache (6%), pneumonia (5%), stomatitis (5%), rash (4%), blood creatinine increase (4%), pneumonitis (2%), upper abdominal pain (2%), and hypersensitivity (1%).</paragraph>
<table width="100%">
<caption>Table 15 Laboratory Abnormalities Reported in ≥25% of Patients in PROfound</caption>
<col width="39%"/>
<col width="16%"/>
<col width="14%"/>
<col width="16%"/>
<col width="15%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<paragraph>
<content styleCode="bold">Laboratory<br/>Parameter</content>
<footnote ID="_Ref96937425">Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.</footnote>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza tablets</content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnote ID="_Ref40249547">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
<content styleCode="bold">= 256</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Enzalutamide or abiraterone </content>
</paragraph>
<paragraph>
<content styleCode="bold">n</content>
<footnoteRef IDREF="_Ref40249547"/>
<content styleCode="bold">=130</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in hemoglobin</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>98</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>73</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in lymphocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>62</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>34</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in leukocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>53</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>21</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>Decrease in absolute neutrophil count</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>34</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="underline">Treatment of <content styleCode="italics">BRCA</content>-mutated Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone</content>
</paragraph>
<paragraph>
<content styleCode="italics">PROpel</content>
</paragraph>
<paragraph>The safety of Lynparza in combination with abiraterone and prednisone or prednisolone for the treatment of patients in the first-line mCRPC setting was investigated in PROpel <content styleCode="italics">[see <linkHtml href="#ID_839b59a7-f0fa-4d99-9e9d-9ce0f90e9470">Clinical Studies (14.8)</linkHtml>]</content>. Patients were randomized to receive either Lynparza tablets 300 mg orally twice daily plus abiraterone tablets 1000 mg once daily (Lynparza/abiraterone) (n=398), or placebo plus abiraterone 1000 mg once daily (placebo/abiraterone) (n=396) until disease progression or unacceptable toxicity. Patients in both arms also received either prednisone or prednisolone 5 mg twice daily.</paragraph>
<paragraph>Fatal adverse reactions occurred in 6% of patients, including COVID-19 (3%) and pneumonias (0.5%). </paragraph>
<paragraph>Serious adverse reactions occurred in 39% of patients. Serious adverse reactions reported in > 2% of patients included anemia (6%), COVID-19 (6%), pneumonia (4.5%), pulmonary embolism (3.5%), and urinary tract infection (3%).</paragraph>
<paragraph>Permanent discontinuation of Lynparza due to adverse reactions occurred in 16% of patients treated in the Lynparza with abiraterone arm. The most common adverse reactions which resulted in permanent discontinuation of Lynparza were anemia (4.3%) and pneumonia (1.5%).</paragraph>
<paragraph>Dosage interruption of Lynparza due to adverse reactions occurred in 48% of patients treated in the Lynparza with abiraterone arm. The most common (>2%) adverse reactions requiring dosage interruption of Lynparza were anemia (16%), COVID-19 (6%) fatigue (3.5%), nausea (2.8%), pulmonary embolism (2.3%), and diarrhea (2.3%). </paragraph>
<paragraph>Dose reduction of Lynparza due to adverse reactions occurred in 21% of patients treated in the Lynparza with abiraterone arm. The most common (>2%) adverse reactions requiring dosage reductions of Lynparza were anemia (11%) and fatigue (2.5%).</paragraph>
<paragraph>The most common adverse reactions (≥10%) in patients who received Lynparza/abiraterone were anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), abdominal pain (13%), and dizziness (14%). </paragraph>
<paragraph>Tables 16 and 17 summarize adverse reactions and laboratory abnormalities in PROpel, respectively.</paragraph>
<table width="100%">
<caption>Table 16 Adverse Reactions (≥10%) in Patients Who Received Lynparza (with a Difference of ≥5% Compared to Placebo) in PROpel</caption>
<col width="35%"/>
<col width="16%"/>
<col width="15%"/>
<col width="17%"/>
<col width="16%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Adverse Reactions</content>
<footnote ID="_Ref136517653">Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.</footnote>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza/abiraterone<br/>n=398</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo/abiraterone<br/>n=396</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and Lymphatic Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Anemia<footnote ID="_Ref136517698">Includes anemia, anemia macrocytic, and red blood cell count decreased</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>48</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>3.3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Lymphopenia<footnote ID="_Ref136517709">Includes lymphocyte count decreased and lymphopenia</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1.8</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Fatigue (including asthenia)</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>38</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>2.3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1.5</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Abdominal pain<footnote ID="_Ref136517721">Includes abdominal discomfort, abdominal pain, abdominal pain upper, and abdominal pain lower</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.5</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Metabolism and nutrition disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Decreased appetite</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="5" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Nervous System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph> Dizziness<footnote ID="_Ref136517732">Includes dizziness and vertigo.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0.3</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions that occurred in <10% for patients receiving Lynparza plus abiraterone were headache (9%), VTE (8%), rash (7%), dysgeusia (6%), acute kidney injury (3%), and stomatitis (2.5%).</paragraph>
<table width="100%">
<caption>Table 17 Selected Laboratory Abnormalities Reported in ≥20% of Patients in PROpel</caption>
<col width="25%"/>
<col width="19%"/>
<col width="17%"/>
<col width="20%"/>
<col width="18%"/>
<tbody>
<tr>
<td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Laboratory Parameter</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Lynparza/abiraterone<br/>n=398<footnote ID="_Ref136519297">This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.</footnote>
</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Placebo/abiraterone <br/>n=396</content>
<footnoteRef IDREF="_Ref136519297"/>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 1-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grades 3-4</content>
</paragraph>
<paragraph>
<content styleCode="bold">(%)</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in hemoglobin</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>97</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>81</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1.3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in lymphocytes</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>70</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>49</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Decrease in platelets </paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>1.2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>0.3</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>Decrease in absolute neutrophil count</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
</text>
<effectiveTime value="20231106"/>
</section>
</component>
<component>
<section ID="ID_d93b615f-46ed-49a4-988c-59a9e5ffeb6e">
<id root="bade9299-639e-4de7-b909-3d94a03afa4f"/>
<code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
<title>6.2 Postmarketing Experience </title>
<text>
<paragraph>The following adverse reactions have been identified during post-approval use of Lynparza. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.</paragraph>
<paragraph>
<content styleCode="italics">Immune System Disorders</content>: Hypersensitivity including angioedema.</paragraph>
<paragraph>
<content styleCode="italics">Skin and subcutaneous tissue disorders</content>: Erythema nodosum, rash, dermatitis.</paragraph>
</text>
<effectiveTime value="20231106"/>
</section>
</component>
</section>