<?xml version="1.0" encoding="UTF-8"?><section ID="ID_808ee5e2-a73c-4545-98b2-60a1527f3935">
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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 in more detail in other sections of the labeling:</paragraph>
<list listType="unordered">
<item>
<caption>•</caption>Risk of Bleeding <content styleCode="italics">[see <linkHtml href="#williamsonbk1284602429423">Warnings and Precautions (5.1)</linkHtml>]</content>
</item>
<item>
<caption>•</caption>Increased Exposure in Patients with Hepatic Impairment <content styleCode="italics">[see <linkHtml href="#williamsonbk1284491220285">Warnings and Precautions (5.2)</linkHtml>]</content>
</item>
<item>
<caption>•</caption>Injection Site Reaction <content styleCode="italics">[see <linkHtml href="#ID_79c1ecf5-da5e-462b-bfe3-cfe69936accc">Warnings and Precautions (5.3)</linkHtml>]</content>
</item>
<item>
<caption>•</caption>Embryo-Fetal Toxicity <content styleCode="italics">[see <linkHtml href="#williamsonbk1284602321124">Warnings and Precautions (5.4)</linkHtml>]</content>
</item>
</list>
</text>
<effectiveTime value="20200925"/>
<excerpt>
<highlight>
<text>
<list listType="unordered">
<item>
<caption>•</caption>The most common adverse reactions occurring in ≥5% of patients receiving FASLODEX 500 mg were: injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and constipation. <linkHtml href="#_Ref">(6.1)</linkHtml>
</item>
<item>
<caption>•</caption>Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX patients and were not dose-dependent. <linkHtml href="#_Ref">(6.1)</linkHtml>
</item>
</list>
<paragraph>
<content styleCode="bold">To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 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_33357c92-12cd-4692-9851-4045a88dc94c">
<id root="56bc62db-1b86-4a0e-9c06-015907081f87"/>
<code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
<title>6.1 Clinical Trials Experience </title>
<text>
<paragraph>Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.</paragraph>
<paragraph>
<content styleCode="bold">
<content styleCode="underline">Monotherapy</content>
</content>
</paragraph>
<paragraph>
<content styleCode="bold">
<content styleCode="underline">Comparison of FASLODEX 500 mg and FASLODEX 250 mg (CONFIRM)</content>
</content>
</paragraph>
<paragraph>The following adverse reactions (ARs) were calculated based on the safety analysis of CONFIRM comparing the administration of FASLODEX 500 mg intramuscularly once a month with FASLODEX 250 mg intramuscularly once a month. The most frequently reported adverse reactions in the FASLODEX 500 mg group were injection site pain (11.6% of patients), nausea (9.7% of patients), and bone pain (9.4% of patients); the most frequently reported adverse reactions in the FASLODEX 250 mg group were nausea (13.6% of patients), back pain (10.7% of patients), and injection site pain (9.1% of patients).</paragraph>
<paragraph>Table 1 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from CONFIRM.</paragraph>
<table ID="_RefID0EVIAE" width="100%">
<caption>Table 1: Adverse Reactions in CONFIRM (≥5% in Either Treatment Group)</caption>
<col width="33%"/>
<col width="34%"/>
<col width="34%"/>
<tbody>
<tr>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Adverse Reactions</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">FASLODEX 500 mg </content>
</paragraph>
<paragraph>
<content styleCode="bold">N=361</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">FASLODEX 250 mg</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=374</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="3" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Body as a Whole</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Injection Site Pain<footnote ID="_Ref452094659">Including more severe injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Headache</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Back Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Fatigue</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Pain in Extremity</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Asthenia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td colspan="3" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Vascular System</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Hot Flash</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td colspan="3" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Digestive System</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Anorexia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Constipation</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
</tr>
<tr>
<td colspan="3" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Musculoskeletal System</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Bone Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Arthralgia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Musculoskeletal Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
</tr>
<tr>
<td colspan="3" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Respiratory System</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Cough</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>Dyspnea</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>In the pooled safety population (N=1127) from clinical trials comparing FASLODEX 500 mg to FASLODEX 250 mg, post-baseline increases of ≥1 CTC grade in either AST, ALT, or alkaline phosphatase were observed in >15% of patients receiving FASLODEX. Grade 3-4 increases were observed in 1-2% of patients. The incidence and severity of increased hepatic enzymes (ALT, AST, ALP) did not differ between the 250 mg and the 500 mg FASLODEX arms.</paragraph>
<paragraph>
<content styleCode="bold">
<content styleCode="underline">Comparison of FASLODEX 500 mg and Anastrozole 1 mg (FALCON)</content>
</content>
</paragraph>
<paragraph>The safety of FASLODEX 500 mg versus anastrozole 1 mg was evaluated in FALCON. The data described below reflect exposure to FASLODEX in 228 out of 460 patients with HR-positive advanced breast cancer in postmenopausal women not previously treated with endocrine therapy who received at least one (1) dose of treatment in FALCON.</paragraph>
<paragraph>Permanent discontinuation associated with an adverse reaction occurred in 4 of 228 (1.8%) patients receiving FASLODEX and in 3 of 232 (1.3%) patients receiving anastrozole. Adverse reactions leading to discontinuation for those patients receiving FASLODEX included drug hypersensitivity (0.9%), injection site hypersensitivity (0.4%), and elevated liver enzymes (0.4%).</paragraph>
<paragraph>The most common adverse reactions (≥10%) of any grade reported in patients in the FASLODEX arm were arthralgia, hot flash, fatigue, and nausea.</paragraph>
<paragraph>Adverse reactions reported in patients who received FASLODEX in FALCON at an incidence of ≥5% in either treatment arm are listed in Table 2, and laboratory abnormalities are listed in Table 3.</paragraph>
<table ID="_RefID0EGTAE" width="100%">
<caption>Table 2: Adverse Reactions in FALCON</caption>
<col width="20%"/>
<col width="20%"/>
<col width="20%"/>
<col width="20%"/>
<col width="20%"/>
<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">FASLODEX 500 mg</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=228</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Anastrozole 1 mg</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=232</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 3 or 4</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 3 or 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">Vascular Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Hot flash</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule 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 Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule 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 Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</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</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Myalgia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Pain in extremity</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Back pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule 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 Botrule Lrule " valign="top">
<paragraph>Fatigue</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph><1</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph> </paragraph>
<table ID="_RefID0EF4AE" width="97.06%">
<caption>Table 3: Laboratory Abnormalities in FALCON<footnote ID="_Ref464825266">In FALCON, post-baseline increases of ≥1 CTC grade in either AST, ALT, or alkaline phosphatase were observed in >10% of patients receiving FASLODEX. Grade 3-4 increases were observed in 1%-3% of patients.</footnote>
</caption>
<col width="28%"/>
<col width="26%"/>
<col width="25%"/>
<col width="10%"/>
<col width="11%"/>
<tbody>
<tr>
<td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Laboratory Parameters</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">FASLODEX 500 mg</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=228</content>
</paragraph>
</td>
<td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Anastrozole 1 mg</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=232</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 3 or 4</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 3 or 4</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Alanine aminotransferase increased (ALT)</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>Aspartate aminotransferase increased (AST)</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph><1</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="bold">
<content styleCode="underline">Comparison of FASLODEX 250 mg and Anastrozole 1 mg in Combined Trials (Studies 0020 and 0021)</content>
</content>
</paragraph>
<paragraph>The most commonly reported adverse reactions in the FASLODEX and anastrozole treatment groups were gastrointestinal symptoms (including nausea, vomiting, constipation, diarrhea, and abdominal pain), headache, back pain, vasodilatation (hot flashes), and pharyngitis.</paragraph>
<paragraph>Injection site reactions with mild transient pain and inflammation were seen with FASLODEX and occurred in 7% of patients given the single 5 mL injection (Study 0020) and in 27% of patients given the 2 x 2.5 mL injections (Study 0021) in the two clinical trials that compared FASLODEX 250 mg and anastrozole 1 mg.</paragraph>
<paragraph>Table 4 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from the two controlled clinical trials comparing the administration of FASLODEX 250 mg intramuscularly once a month with anastrozole 1 mg orally once a day.</paragraph>
<table ID="_RefID0EZBAG" width="100%">
<caption>Table 4: Adverse Reactions in Studies 0020 and 0021 (≥5% from Combined Data)</caption>
<col width="48%"/>
<col width="28%"/>
<col width="24%"/>
<thead>
<tr>
<th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">Adverse Reactions</content>
</th>
<th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">FASLODEX 250 mg </content>
<br/>
<content styleCode="bold">N=423 </content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">Anastrozole 1 mg </content>
<br/>
<content styleCode="bold">N=423 </content>
<br/>
<content styleCode="bold">%</content>
</th>
</tr>
</thead>
<tbody>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Body as a Whole</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>68</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>68</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Asthenia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>27</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Headache</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Back Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Abdominal Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Injection Site Pain<footnote ID="_Ref432408817">Including more severe injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy. All patients on FASLODEX received injections, but only those anastrozole patients who were in Study 0021 received placebo injections.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Pelvic Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Chest Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Flu Syndrome</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Fever</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Accidental Injury</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Cardiovascular System</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>28</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Vasodilatation</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Digestive System</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>52</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>48</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>26</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>25</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Constipation</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Anorexia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Hemic and Lymphatic Systems</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Anemia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Metabolic and Nutritional Disorders</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Peripheral Edema</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Musculoskeletal System </content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>26</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>28</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Bone Pain</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>14</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Arthritis</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Nervous System</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>34</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>34</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Dizziness</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Insomnia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Paresthesia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Depression</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Anxiety</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Respiratory System</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>39</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>34</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Pharyngitis</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Dyspnea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Cough Increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Skin and Appendages</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Rash</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Sweating</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Urogenital System</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>Urinary Tract Infection</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>4</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="bold">
<content styleCode="underline">Combination Therapy</content>
</content>
</paragraph>
<paragraph>
<content styleCode="bold">
<content styleCode="underline">Combination Therapy with Palbociclib (PALOMA-3)</content>
</content>
</paragraph>
<paragraph>The safety of FASLODEX 500 mg plus palbociclib 125 mg/day versus FASLODEX plus placebo was evaluated in PALOMA-3. The data described below reflect exposure to FASLODEX plus palbociclib in 345 out of 517 patients with HR-positive, HER2-negative advanced or metastatic breast cancer who received at least 1 dose of treatment in PALOMA-3. The median duration of treatment for FASLODEX plus palbociclib was 10.8 months while the median duration of treatment for FASLODEX plus placebo arm was 4.8 months.</paragraph>
<paragraph>No dose reduction was allowed for FASLODEX in PALOMA-3. Dose reductions of palbociclib due to an adverse reaction of any grade occurred in 36% of patients receiving FASLODEX plus palbociclib.</paragraph>
<paragraph>Permanent discontinuation associated with an adverse reaction occurred in 19 of 345 (6%) patients receiving FASLODEX plus palbociclib, and in 6 of 172 (3%) patients receiving FASLODEX plus placebo. Adverse reactions leading to discontinuation for those patients receiving FASLODEX plus palbociclib included fatigue (0.6%), infections (0.6%), and thrombocytopenia (0.6%).</paragraph>
<paragraph>The most common adverse reactions (≥10%) of any grade reported in patients in the FASLODEX plus palbociclib arm by descending frequency were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting, alopecia, rash, decreased appetite, and pyrexia.</paragraph>
<paragraph>The most frequently reported Grade ≥3 adverse reactions (≥5%) in patients receiving FASLODEX plus palbociclib in descending frequency were neutropenia and leukopenia.</paragraph>
<paragraph>Adverse reactions (≥10%) reported in patients who received FASLODEX plus palbociclib or FASLODEX plus placebo in PALOMA-3 are listed in Table 5, and laboratory abnormalities are listed in Table 6.</paragraph>
<table ID="_RefID0EAYAG" cellpadding="3.6pt" width="100%">
<caption>Table 5: Adverse Reactions (≥10%) in PALOMA-3</caption>
<col width="21%"/>
<col width="21%"/>
<col width="21%"/>
<col width="9%"/>
<col width="9%"/>
<col width="9%"/>
<col width="9%"/>
<thead>
<tr>
<th align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<content styleCode="bold">Adverse Reactions</content>
</th>
<th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="bottom">
<content styleCode="bold">FASLODEX plus Palbociclib</content>
<br/>
<content styleCode="bold">N=345</content>
</th>
<th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="bottom">
<content styleCode="bold">FASLODEX plus Placebo </content>
<br/>
<content styleCode="bold">N=172</content>
</th>
</tr>
<tr>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">All Grades</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 3</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 4</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">All Grades</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 3</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 4</content>
<br/>
<content styleCode="bold">%</content>
</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="7" styleCode="Rrule Lrule Toprule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Infections and Infestations</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Infections<footnote ID="_Ref445107416">Infections includes all reported preferred terms (PTs) that are part of the System Organ Class Infections and infestations.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>47<footnote ID="_Ref500236166">Most common infections (≥1%) include: nasopharyngitis, upper respiratory infection, urinary tract infection, influenza, bronchitis, rhinitis, conjunctivitis, pneumonia, sinusitis, cystitis, oral herpes, respiratory tract infection, gastroenteritis, tooth infection, pharyngitis, eye infection, herpes simplex, paronychia.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>31</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Blood and Lymphatic System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Neutropenia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>83</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>55</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Leukopenia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>53</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Anemia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Thrombocytopenia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Metabolism and Nutrition Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Decreased appetite</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>34</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Stomatitis<footnote ID="_Ref464829251">Stomatitis includes: aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal discomfort, oropharyngeal pain, stomatitis.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>24</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Alopecia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>18<footnote ID="_Ref464829289">Grade 1 events – 17%; Grade 2 events – 1%.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>N/A</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>N/A</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>6<footnote ID="_Ref464829306">Grade 1 events – 6%.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>N/A</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>N/A</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Rash<footnote ID="_Ref464829320">Rash includes: rash, rash maculo-papular, rash pruritic, rash erythematous, rash papular, dermatitis, dermatitis acneiform, toxic skin eruption.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Fatigue</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>41</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>29</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Pyrexia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Botrule " valign="bottom">
<paragraph>Grading according to CTCAE v.4.0.</paragraph>
<paragraph>CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients; N/A=not applicable.</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Additional adverse reactions occurring at an overall incidence of <10.0% of patients receiving FASLODEX plus palbociclib in PALOMA-3 included asthenia (7.5%), aspartate aminotransferase increased (7.5%), dysgeusia (6.7%), epistaxis (6.7%), lacrimation increased (6.4%), dry skin (6.1%), alanine aminotransferase increased (5.8%), vision blurred (5.8%), dry eye (3.8%), and febrile neutropenia (0.9%). </paragraph>
<table ID="_RefID0E1MBG" cellpadding="5.75pt" width="100%">
<caption>Table 6: Laboratory Abnormalities in PALOMA-3</caption>
<col width="20%"/>
<col width="20%"/>
<col width="20%"/>
<col width="11%"/>
<col width="10%"/>
<col width="10%"/>
<col width="10%"/>
<thead>
<tr>
<th align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<content styleCode="bold">Laboratory Parameters</content>
</th>
<th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<content styleCode="bold">FASLODEX plus Palbociclib</content>
<br/>
<content styleCode="bold">N=345</content>
</th>
<th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle">
<content styleCode="bold">FASLODEX plus Placebo</content>
<br/>
<content styleCode="bold">N=172</content>
</th>
</tr>
<tr>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">All Grades</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 3</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 4</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">All Grades</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 3</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 4</content>
<br/>
<content styleCode="bold">%</content>
</th>
</tr>
</thead>
<tbody>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>WBC decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>99</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>45</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle">
<paragraph>26</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>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>Neutrophils decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>96</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>56</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>Anemia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>78</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>3 </paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>40</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>Platelets decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>62</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>Aspartate aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>43</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>48</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule " valign="middle">
<paragraph>Alanine aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="middle">
<paragraph>36</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="middle">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="middle">
<paragraph>34</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>N=number of patients; WBC=white blood cells.</paragraph>
<paragraph>
<content styleCode="bold">
<content styleCode="underline">Combination Therapy with Abemaciclib (MONARCH 2)</content>
</content>
</paragraph>
<paragraph>The safety of FASLODEX (500 mg) plus abemaciclib (150 mg twice daily) versus FASLODEX plus placebo was evaluated in MONARCH 2. The data described below reflect exposure to FASLODEX in 664 patients with HR-positive, HER2-negative advanced breast cancer who received at least one dose of FASLODEX plus abemaciclib or placebo in MONARCH 2.</paragraph>
<paragraph>Median duration of treatment was 12 months for patients receiving FASLODEX plus abemaciclib and 8 months for patients receiving FASLODEX plus placebo.</paragraph>
<paragraph>Dose reductions due to an adverse reaction occurred in 43% of patients receiving FASLODEX plus abemaciclib. Adverse reactions leading to dose reductions ≥5% of patients were diarrhea and neutropenia. Abemaciclib dose reduction due to diarrhea of any grade occurred in 19% of patients receiving FASLODEX plus abemaciclib compared to 0.4% of patients receiving FASLODEX plus placebo. Abemaciclib dose reductions due to neutropenia of any grade occurred in 10% of patients receiving FASLODEX plus abemaciclib compared to no patients receiving FASLODEX plus placebo. </paragraph>
<paragraph>Permanent study treatment discontinuation due to an adverse event was reported in 9% of patients receiving FASLODEX plus abemaciclib and in 3% of patients receiving FASLODEX plus placebo. Adverse reactions leading to permanent discontinuation for patients receiving FASLODEX plus abemaciclib were infection (2%), diarrhea (1%), hepatotoxicity (1%), fatigue (0.7%), nausea (0.2%), abdominal pain (0.2%), acute kidney injury (0.2%), and cerebral infarction (0.2%).</paragraph>
<paragraph>Deaths during treatment or during the 30-day follow up, regardless of causality, were reported in 18 cases (4%) of FASLODEX plus abemaciclib treated patients versus 10 cases (5%) of FASLODEX plus placebo treated patients. Causes of death for patients receiving FASLODEX plus abemaciclib included: 7 (2%) patient deaths due to underlying disease, 4 (0.9%) due to sepsis, 2 (0.5%) due to pneumonitis, 2 (0.5%) due to hepatotoxicity, and one (0.2%) due to cerebral infarction.</paragraph>
<paragraph>The most common adverse reactions reported (≥20%) in the FASLODEX plus abemaciclib arm were diarrhea, fatigue, neutropenia, nausea, infections, abdominal pain, anemia, leukopenia, decreased appetite, vomiting, and headache (Table 7). The most frequently reported (≥5%) Grade 3 or 4 adverse reactions were neutropenia, diarrhea, leukopenia, anemia, and infections.</paragraph>
<table ID="_RefID0E2WBG" width="100%">
<caption>Table 7: Adverse Reactions ≥10% of Patients Receiving FASLODEX Plus Abemaciclib and ≥2% Higher Than FASLODEX Plus Placebo in MONARCH 2</caption>
<col width="45%"/>
<col width="11%"/>
<col width="9%"/>
<col width="8%"/>
<col width="10%"/>
<col width="9%"/>
<col width="8%"/>
<tbody>
<tr>
<td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">Adverse Reactions</content>
</paragraph>
</td>
<td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">FASLODEX plus Abemaciclib</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=441</content>
</paragraph>
</td>
<td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">FASLODEX plus Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=223</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top"/>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade</content>
</paragraph>
<paragraph>
<content styleCode="bold">3</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 4</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade</content>
</paragraph>
<paragraph>
<content styleCode="bold">3</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 4</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="7" 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> Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>86</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>25</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>45</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Abdominal pain<footnote ID="_Ref495579807">Includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, abdominal tenderness.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule 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 Botrule " valign="top">
<paragraph>26</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Stomatitis</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" 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> Infections<footnote ID="_Ref495579980">Includes upper respiratory tract infection, urinary tract infection, lung infection, pharyngitis, conjunctivitis, sinusitis, vaginal infection, sepsis.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>43</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>25</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Blood and Lymphatic System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Neutropenia<footnote ID="_Ref495580016">Includes neutropenia, neutrophil count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>46</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>24</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Anemia<footnote ID="_Ref495580206">Includes anemia, hematocrit decreased, hemoglobin decreased, red blood cell count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>29</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Leukopenia<footnote ID="_Ref495580226">Includes leukopenia, white blood cell count decreased.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>9</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Thrombocytopenia<footnote ID="_Ref495580255">Includes platelet count decreased, thrombocytopenia.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
</tr>
<tr>
<td colspan="7" 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<footnote ID="_Ref495580291">Includes asthenia, fatigue.</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>46</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>32</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Edema peripheral</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Pyrexia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" 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 Botrule " valign="top">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" 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 Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Alopecia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Pruritus</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Rash</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" 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> Headache</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Dysgeusia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Dizziness</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Investigations</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Alanine aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Aspartate aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph> Creatinine increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule " valign="top">
<paragraph> Weight decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>10</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Additional adverse reactions in MONARCH 2 include venous thromboembolic events (deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian vein thrombosis, axillary vein thrombosis, and DVT inferior vena cava), which were reported in 5% of patients treated with FASLODEX plus abemaciclib as compared to 0.9% of patients treated with FASLODEX plus placebo.</paragraph>
<table ID="_RefID0E2YAI" width="100%">
<caption>Table 8: Laboratory Abnormalities ≥10% in Patients Receiving FASLODEX Plus Abemaciclib and ≥2% Higher Than FASLODEX Plus Placebo in MONARCH 2</caption>
<col width="35%"/>
<col width="12%"/>
<col width="10%"/>
<col width="10%"/>
<col width="13%"/>
<col width="10%"/>
<col width="10%"/>
<thead>
<tr>
<th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">Laboratory Parameters</content>
</th>
<th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">Fulvestrant plus Abemaciclib</content>
<br/>
<content styleCode="bold">N=441</content>
</th>
<th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">Fulvestrant plus Placebo</content>
<br/>
<content styleCode="bold">N=223</content>
</th>
</tr>
<tr>
<th align="left" styleCode="Rrule Lrule Botrule " valign="middle"/>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">All Grades</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 3</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 4</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">All Grades</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 3</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 4</content>
<br/>
<content styleCode="bold">%</content>
</th>
</tr>
</thead>
<tbody>
<tr>
<td styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>Creatinine increased</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>1</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>74</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>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>White blood cell decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>90</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>33</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Neutrophil count decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>87</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>29</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Anemia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>84</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>33</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Lymphocyte count decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>63</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>32</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Platelet count decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>53</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Alanine aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>41</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>32</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>Aspartate aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>37</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>25</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph><1</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>
<content styleCode="bold">
<content styleCode="underline">Combination Therapy with Ribociclib (MONALEESA-3)</content>
</content>
</paragraph>
<paragraph>The safety of FASLODEX 500 mg plus ribociclib 600 mg versus FASLODEX plus placebo was evaluated in MONALEESA-3. The data described below reflect exposure to FASLODEX plus ribociclib in 483 out of 724 postmenopausal patients with HR-positive, HER2-negative advanced or metastatic breast cancer for initial endocrine based therapy or after disease progression on endocrine therapy who received at least one dose of FASLODEX plus ribociclib or placebo in MONALEESA-3. Median duration of treatment was 15.8 months for FASLODEX plus ribociclib and 12 months for FASLODEX plus placebo.</paragraph>
<paragraph>Dose reductions due to adverse reactions occurred in 32% of patients receiving FASLODEX plus ribociclib and in 3% of patients receiving FASLODEX plus placebo. Among patients receiving FASLODEX plus ribociclib, 8% were reported to have permanently discontinued both FASLODEX plus ribociclib, and 9% were reported to have discontinued ribociclib alone due to ARs. Among patients receiving FASLODEX plus placebo, 4% were reported to have permanently discontinued both FASLODEX and placebo and 2% were reported to have discontinued placebo alone due to ARs.</paragraph>
<paragraph>Adverse reactions leading to treatment discontinuation of FASLODEX plus ribociclib (as compared to FASLODEX plus placebo) were ALT increased (5% vs. 0%), AST increased (3% vs. 0.6%), and vomiting (1% vs. 0%).</paragraph>
<paragraph>The most common adverse reactions (reported at a frequency ≥20% on the FASLODEX plus ribociclib arm and ≥2% higher than FASLODEX plus placebo) were neutropenia, infections, leukopenia, cough, nausea, diarrhea, vomiting, constipation, pruritus, and rash. The most frequently reported Grade 3/4 adverse reactions (reported at a frequency ≥5%) in patients receiving FASLODEX plus ribociclib in descending frequency were neutropenia, leukopenia, infections, and abnormal liver function tests.</paragraph>
<paragraph>Adverse reactions and laboratory abnormalities occurring in patients in MONALEESA-3 are listed in Table 9 and Table 10, respectively.</paragraph>
<table ID="_RefID0EGFBI" width="100%">
<caption>Table 9: Adverse Reactions Occurring in ≥10% and ≥2% higher than FASLODEX plus Placebo Arm in MONALEESA-3 (All Grades)</caption>
<col width="20%"/>
<col width="20%"/>
<col width="19%"/>
<col width="10%"/>
<col width="10%"/>
<col width="10%"/>
<col width="10%"/>
<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="3" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">FASLODEX plus Ribociclib</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=483</content>
</paragraph>
</td>
<td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<paragraph>
<content styleCode="bold">FASLODEX plus Placebo</content>
</paragraph>
<paragraph>
<content styleCode="bold">N=241</content>
</paragraph>
</td>
</tr>
<tr>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 3</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 4</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">All Grades</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 3</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Grade 4</content>
</paragraph>
<paragraph>
<content styleCode="bold">%</content>
</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Infections and Infestations</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Infections<footnote ID="_Ref3878295">Infections; urinary tract infections; respiratory tract infections; gastroenteritis; sepsis (<1%).</footnote>
</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>42</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>30</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Blood and Lymphatic System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Neutropenia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>69</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>46</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Leukopenia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Anemia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Metabolism and Nutrition Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Decreased appetite</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>16</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Nervous System Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Dizziness</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Respiratory, Thoracic, and Mediastinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Cough</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>22</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Dyspnea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Gastrointestinal Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Nausea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>45</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>28</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Diarrhea</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>29</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Vomiting</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>27</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Constipation</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>25</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Abdominal pain </paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>17</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Alopecia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>19</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Pruritus</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>20</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Rash</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Edema peripheral</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Pyrexia</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>
<content styleCode="bold">Investigations</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Alanine aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>15</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="bottom">
<paragraph>Aspartate aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>13</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Botrule " valign="bottom">
<paragraph>Grading according to CTCAE 4.03.</paragraph>
<paragraph>CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients</paragraph>
</td>
</tr>
</tbody>
</table>
<paragraph>Additional adverse reactions in MONALEESA-3 for patients receiving FASLODEX plus ribociclib included asthenia (14%), dyspepsia (10%), thrombocytopenia (9%), dry skin (8%), dysgeusia (7%), electrocardiogram QT prolonged (6%), dry mouth (5%), vertigo (5%), dry eye (5%), lacrimation increased (4%), erythema (4%), hypocalcemia (4%), blood bilirubin increased (1%), and syncope (1%).</paragraph>
<table ID="_RefID0E4BCI" width="100%">
<caption>Table 10: Laboratory Abnormalities Occurring in ≥10% of Patients in MONALEESA-3</caption>
<col width="21%"/>
<col width="20%"/>
<col width="19%"/>
<col width="9%"/>
<col width="10%"/>
<col width="10%"/>
<col width="9%"/>
<thead>
<tr>
<th align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">Laboratory parameters</content>
</th>
<th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">FASLODEX plus Ribociclib</content>
<br/>
<content styleCode="bold">N=483</content>
</th>
<th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top">
<content styleCode="bold">FASLODEX plus Placebo </content>
<br/>
<content styleCode="bold">N=241</content>
</th>
</tr>
<tr>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">All Grades</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 3</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 4</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">All Grades</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 3</content>
<br/>
<content styleCode="bold">%</content>
</th>
<th align="center" styleCode="Rrule Lrule Botrule " valign="top">
<content styleCode="bold">Grade 4</content>
<br/>
<content styleCode="bold">%</content>
</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="7" styleCode="Rrule Lrule Toprule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Hematology</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Leukocyte count decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>95</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>25</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>26</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Neutrophil count decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>92</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>46</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>7</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>21</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Hemoglobin decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>60</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Lymphocyte count decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>69</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>14</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>35</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>4</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Platelet count decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>33</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>11</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="middle">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td colspan="7" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>
<content styleCode="bold">Chemistry</content>
</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Creatinine increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>65</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>33</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Gamma-glutamyl transferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>52</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>6</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>49</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Aspartate aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>49</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>43</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Alanine aminotransferase increased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>44</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>3</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>37</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>2</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Glucose serum decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>23</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>Phosphorous decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>18</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>5</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph><1</paragraph>
</td>
<td align="center" styleCode="Rrule Lrule Botrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
<tr>
<td styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>Albumin decreased</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>12</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>8</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>0</paragraph>
</td>
<td align="center" styleCode="Rrule Botrule Lrule " valign="top">
<paragraph>0</paragraph>
</td>
</tr>
</tbody>
</table>
</text>
<effectiveTime value="20200925"/>
</section>
</component>
<component>
<section ID="ID_c8467fea-c807-4076-a24e-220394240b8a">
<id root="6b901ed0-9ef3-4270-8c33-7a9753cae180"/>
<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 FASLODEX. 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>For FASLODEX 250 mg, other adverse reactions reported as drug-related and seen infrequently (<1%) include thromboembolic phenomena, myalgia, vertigo, leukopenia, and hypersensitivity reactions, including angioedema and urticaria.</paragraph>
<paragraph>Vaginal bleeding has been reported infrequently (<1%), mainly in patients during the first 6 weeks after changing from existing hormonal therapy to treatment with FASLODEX. If bleeding persists, further evaluation should be considered.</paragraph>
<paragraph>Elevation of bilirubin, elevation of gamma GT, hepatitis, and liver failure have been reported infrequently (<1%).</paragraph>
</text>
<effectiveTime value="20200513"/>
</section>
</component>
</section>