TUKYSA

5 WARNINGS AND PRECAUTIONS • Diarrhea : Severe diarrhea, including dehydration, acute kidney injury, and death, has been reported. Administer antidiarrheal treatment as clinically indicated. Interrupt dose, then dose reduce, or permanently discontinue TUKYSA based on severity. ( 2.2 , 5.1 ) • Hepatotoxicity : Severe hepatotoxicity has been reported on TUKYSA. Monitor ALT, AST and bilirubin prior to starting TUKYSA, every 3 weeks during treatment and as clinically indicated. Interrupt dose, then dose reduce, or permanently discontinue TUKYSA based on severity. ( 2.2 , 5.2 ) • Embryo-Fetal Toxicity : TUKYSA can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) Also, refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy and contraception information. 5.1 Diarrhea TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death [see Adverse Reactions (6.1) ] . If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA [see Dosage and Administration (2.2) ] . TUKYSA with trastuzumab and capecitabine In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 diarrhea and 12% with Grade 3 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB. TUKYSA with trastuzumab In MOUNTAINEER, diarrhea occurred in 64% of patients, including Grade 3 (3.5%), Grade 2 (10%), and Grade 1 (50%). 5.2 Hepatotoxicity TUKYSA can cause severe hepatotoxicity [see Adverse Reactions (6.1) ] . Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA [see Dosage and Administration (2.2) ] . TUKYSA with trastuzumab and capecitabine In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase > 5 × ULN, 6% had an AST increase > 5 × ULN, and 1.5% had a bilirubin increase > 3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients. TUKYSA with trastuzumab In MOUNTAINEER, 6% of patients had a bilirubin increase > 3 × ULN (Grade ≥3), 6% had an AST increase > 5 × ULN, and 4.7% had an ALT increase > 5 × ULN. Hepatotoxicity led to dose reduction of TUKYSA in 3.5% of patients and discontinuation of TUKYSA in 2.3% of patients. 5.3 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, TUKYSA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of tucatinib to pregnant rats and rabbits during organogenesis caused embryo-fetal mortality, reduced fetal weight and fetal abnormalities at maternal exposures ≥ 1.3 times the human exposure (AUC) at the recommended dose. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose [see Use in Specific Populations (8.1 , 8.3 )] . TUKYSA is used in combination with trastuzumab and capecitabine. Refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy and contraception information.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Diarrhea [see Warnings and Precautions (5.1) ] • Hepatotoxicity [see Warnings and Precautions (5.2) ] • The most common adverse reactions (≥20%) with TUKYSA in combination with trastuzumab and capecitabine in patients with metastatic breast cancer are diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash. ( 6.1 ) • The most common adverse reactions (≥20%) with TUKYSA in combination with trastuzumab in patients with unresectable or metastatic colorectal cancer are diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia. To report SUSPECTED ADVERSE REACTIONS, contact Seagen at 1-855-4SEAGEN or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. HER2-Positive Metastatic Breast Cancer The safety of TUKYSA in combination with trastuzumab and capecitabine was evaluated in HER2CLIMB [see Clinical Studies (14) ]. Patients received either TUKYSA 300 mg twice daily plus trastuzumab or a non-US approved trastuzumab product, and capecitabine (n=404) or placebo plus trastuzumab or a non-US approved trastuzumab product and capecitabine (n=197). The median duration of treatment was 5.8 months (range: 3 days, 2.9 years) for the TUKYSA arm. Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in ≥ 2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock. Adverse reactions leading to treatment discontinuation occurred in 6% of patients who received TUKYSA. Adverse reactions leading to treatment discontinuation of TUKYSA in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions leading to dose reduction occurred in 21% of patients who received TUKYSA. Adverse reactions leading to dose reduction of TUKYSA in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%). The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash. Table 3 summarizes the adverse reactions in HER2CLIMB. Table 3: Adverse Reactions (≥10%) in Patients Who Received TUKYSA and with a Difference Between Arms of ≥ 5% Compared to Placebo in HER2CLIMB (All Grades) Adverse Reaction TUKYSA + Trastuzumab + Capecitabine N = 404 Placebo + Trastuzumab + Capecitabine N = 197 All Grades % Grade 3 % Grade 4 % All Grades % Grade 3 % Grade 4 % Gastrointestinal disorders Diarrhea 81 12 0.5 53 9 0 Nausea 58 3.7 0 44 3 0 Vomiting 36 3 0 25 3.6 0 Stomatitis Stomatitis includes stomatitis, oropharyngeal pain, oropharyngeal discomfort, mouth ulceration, oral pain, lip ulceration, glossodynia, tongue blistering, lip blister, oral dysesthesia, tongue ulceration, and aphthous ulcer 32 2.5 0 21 0.5 0 Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome 63 13 0 53 9 0 Rash Rash includes rash maculo-papular, rash, dermatitis acneiform, erythema, rash macular, rash papular, rash pustular, rash pruritic, rash erythematous, skin exfoliation, urticaria, dermatitis allergic, palmar erythema, plantar erythema, skin toxicity, and dermatitis 20 0.7 0 15 0.5 0 Hepatobiliary disorders Hepatotoxicity Hepatotoxicity includes hyperbilirubinemia, blood bilirubin increased, bilirubin conjugated increased, alanine aminotransferase increased, transaminases increased, hepatotoxicity, aspartate aminotransferase increased, liver function test increased, liver injury, and hepatocellular injury 42 9 0.2 24 3.6 0 Metabolism and nutrition disorders Decreased appetite 25 0.5 0 20 0 0 Blood and lymphatic system disorders Anemia Anemia includes anemia, hemoglobin decreased, and normocytic anemia 21 3.7 0 13 2.5 0 Musculoskeletal and connective tissue disorders Arthralgia 15 0.5 0 4.6 0.5 0 Investigations Creatinine increased Due to inhibition of renal tubular transport of creatinine without affecting glomerular function 14 0 0 1.5 0 0 Weight decreased 13 1 0 6 0.5 0 Nervous System Disorders Peripheral neuropathy Peripheral neuropathy includes peripheral sensory neuropathy, neuropathy peripheral, peripheral motor neuropathy, and peripheral sensorimotor neuropathy 13 0.5 0 7 1 0 Respiratory, thoracic and mediastinal disorders Epistaxis 12 0 0 5 0 0 Table 4: Laboratory Abnormalities (≥20%) Worsening from Baseline in Patients Who Received TUKYSA and with a Difference of ≥5% Compared to Placebo in HER2CLIMB Laboratory Abnormality TUKYSA + Trastuzumab +Capecitabine The denominator used to calculate the rate varied from 351 to 400 in the TUKYSA arm and 173 to 197 in the control arm based on the number of patients with a baseline value and at least one post-treatment value. Grading was based on NCI-CTCAE v.4.03 for laboratory abnormalities, except for increased creatinine which only includes patients with a creatinine increase based on the upper limit of normal definition for grade 1 events (NCI CTCAE v5.0). Placebo + Trastuzumab +Capecitabine All Grades % Grades ≥3 % All Grades % Grades ≥3 % Hematology Decreased hemoglobin 59 3.3 51 1.5 Chemistry Decreased phosphate 57 8 45 7 Increased bilirubin 47 1.5 30 3.1 Increased ALT 46 8 27 0.5 Increased AST 43 6 25 1 Decreased magnesium 40 0.8 25 0.5 Decreased potassium Laboratory criteria for Grade 1 is identical to laboratory criteria for Grade 2. 36 6 31 5 Increased creatinine Due to inhibition of renal tubular transport of creatinine without affecting glomerular function. 33 0 6 0 Decreased sodium There is no definition for Grade 2 in CTCAE v.4.03. 28 2.5 23 2 Increased alkaline phosphatase 26 0.5 17 0 Increased Creatinine The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed [see Clinical Pharmacology (12.3) ] . RAS Wild-Type, HER2-Positive Unresectable or Metastatic Colorectal Cancer The safety of TUKYSA in combination with trastuzumab or a non-US approved trastuzumab product was evaluated in 86 patients enrolled in MOUNTAINEER with unresectable or metastatic colorectal cancer [see Clinical Studies (14.2) ] . The median duration of exposure to TUKYSA was 6.9 months (range 0.7, 49.3). Serious adverse reactions occurred in 22% of patients. Serious adverse reactions that occurred in ≥ 2% of patients were intestinal obstruction (7%), urinary tract infection (3.5%), pneumonia (2.3%), abdominal pain (2.3%) and rectal perforation (2.3%). Permanent discontinuation of TUKYSA due to an adverse reaction occurred in 6% of patients. The adverse reaction which resulted in permanent discontinuation of TUKYSA in ≥2% of patients was increased ALT (2.3%). Dosage interruptions of TUKYSA due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dosage interruption in ≥3% of patients were increased ALT (3.5%) and diarrhea (3.5%). Dose reductions of TUKYSA due to an adverse reaction occurred in 9% of patients. Adverse reactions which required dose reductions in ≥2% of patients were increased ALT (2.3%) and diarrhea (2.3%). The most common adverse reactions reported in ≥ 20% of patients treated with TUKYSA and trastuzumab were diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia. The most common laboratory abnormalities reported in ≥ 20% of patients were increased creatinine, increased glucose, increased ALT, decreased hemoglobin, increased AST, increased bilirubin, increased alkaline phosphatase, decreased lymphocytes, decreased albumin, decreased leukocytes, and decreased sodium. Table 5 summarizes the adverse reactions in MOUNTAINEER. Table 5: Adverse Reactions (≥10%) in Patients with Unresectable or Metastatic Colorectal Cancer (MOUNTAINEER) Adverse Reaction TUKYSA + Trastuzumab N= 86 Includes 1 patient who only received trastuzumab. All Grades % Grade 3 % Gastrointestinal disorders Diarrhea 64 3.5 Nausea 35 0 Vomiting 16 0 Abdominal pain Abdominal pain includes abdominal discomfort, abdominal pain, and abdominal pain upper. 21 2.3 Constipation 14 1.2 General disorders Fatigue 44 2.3 Pyrexia 20 0 Chills 19 1.2 Skin and subcutaneous disorders Rash Rash includes acne, dermatitis acneiform, dermatitis contact, erythema, erythema multiforme, rash, rash macular, rash maculo-papular, rash papular, rash pustular, skin exfoliation, and urticaria. 37 0 Injury, poisoning, and procedural complications Infusion related reaction 21 0 Metabolism and nutrition disorders Decreased appetite 19 0 Blood and lymphatic system disorders Anemia 10 0 Vascular disorders Hypertension 17 7 Musculoskeletal and connective tissue disorders Back pain 17 2.3 Arthralgia 16 1.2 Myalgia 13 0 Respiratory, thoracic and mediastinal disorders Cough 16 0 Dyspnea 14 0 Psychiatric disorders Anxiety 10 0 Other adverse reactions (<10%) include epistaxis (7%), weight decreased (7%), oropharyngeal pain (5%), oral dysesthesia (1%), and stomatitis (1%). Table 6: Laboratory Abnormalities (≥15%) Worsening from Baseline in Patients with Unresectable or Metastatic Colorectal Cancer (MOUNTAINEER) Laboratory Abnormality TUKYSA + Trastuzumab N=85 Number of patients with both baseline and post-baseline results for each test All Grades % Grade 3 % Grade 4 % Hematology Decreased hemoglobin 46 3.5 0 Decreased lymphocytes 39 12 0 Decreased leukocytes 22 0 0 Decreased platelets 15 0 0 Chemistry Increased creatinine NCI CTCAE v5.0 was used for creatinine increased. NCI CTCAE v4.03 was used for all other laboratory parameters. , Due to inhibition of renal tubular transport of creatinine without affecting glomerular function 58 0 0 Increased glucose 56 2.4 0 Increased ALT 46 2.4 2.4 Increased AST 33 2.4 3.5 Increased bilirubin 28 3.5 2.4 Increased alkaline phosphatase 25 1.2 0 Decreased albumin 24 1.2 0 Decreased sodium 20 6 0 Decreased potassium 16 1.2 0 Increased Creatinine The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible in 87% of patients with values outside normal lab limits upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed [see Clinical Pharmacology (12.3) ] .

<table ID="_RefSPLSERV-8ab90929-cf1e-494a-a3ed-c4ce" width="100%"><caption>Table 3: Adverse Reactions (&#x2265;10%) in Patients Who Received TUKYSA and with a Difference Between Arms of &#x2265; 5% Compared to Placebo in HER2CLIMB (All Grades)</caption><col width="29%"/><col width="12%"/><col width="12%"/><col width="12%"/><col width="12%"/><col width="11%"/><col width="11%"/><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><paragraph><content styleCode="bold">TUKYSA + Trastuzumab + Capecitabine</content></paragraph><paragraph><content styleCode="bold">N = 404</content></paragraph></td><td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><paragraph><content styleCode="bold">Placebo + Trastuzumab + Capecitabine</content></paragraph><paragraph><content styleCode="bold">N = 197</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">Grade 3</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">Grade 4</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">Grade 3</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><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 Toprule Botrule " valign="top"><paragraph>81</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>53</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</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>Nausea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>58</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.7</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>44</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Vomiting </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3</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>25</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Stomatitis<footnote ID="_Ref171610035">Stomatitis includes stomatitis, oropharyngeal pain, oropharyngeal discomfort, mouth ulceration, oral pain, lip ulceration, glossodynia, tongue blistering, lip blister, oral dysesthesia, tongue ulceration, and aphthous ulcer</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>32</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.5</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>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule 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>Palmar-plantar erythrodysesthesia syndrome</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>63</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>53</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Rash<footnote ID="_Ref171610055">Rash includes rash maculo-papular, rash, dermatitis acneiform, erythema, rash macular, rash papular, rash pustular, rash pruritic, rash erythematous, skin exfoliation, urticaria, dermatitis allergic, palmar erythema, plantar erythema, skin toxicity, and dermatitis</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>20</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Hepatobiliary disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hepatotoxicity<footnote ID="_Ref171610064">Hepatotoxicity includes hyperbilirubinemia, blood bilirubin increased, bilirubin conjugated increased, alanine aminotransferase increased, transaminases increased, hepatotoxicity, aspartate aminotransferase increased, liver function test increased, liver injury, and hepatocellular injury</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>42</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule 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 Toprule Botrule " valign="top"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</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>20</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</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>Anemia<footnote ID="_Ref171610073">Anemia includes anemia, hemoglobin decreased, and normocytic anemia</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.7</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>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="7" styleCode="Rrule Lrule Botrule " valign="middle"><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 Toprule Botrule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule 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>Creatinine increased<footnote ID="_Ref171610081">Due to inhibition of renal tubular transport of creatinine without affecting glomerular function</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</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>1.5</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>Weight decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="7" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Nervous System Disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Peripheral neuropathy<footnote ID="_Ref171610088">Peripheral neuropathy includes peripheral sensory neuropathy, neuropathy peripheral, peripheral motor neuropathy, and peripheral sensorimotor neuropathy</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="7" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Epistaxis</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0</paragraph></td></tr></tbody></table>

<table ID="_RefID0EJVAG" styleCode="Noautorules" width="80%"><caption>Table 4: Laboratory Abnormalities (&#x2265;20%) Worsening from Baseline in Patients Who Received TUKYSA and with a Difference of &#x2265;5% Compared to Placebo in HER2CLIMB</caption><col width="31%"/><col width="15%"/><col width="15%"/><col width="15%"/><col width="15%"/><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Laboratory Abnormality</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">TUKYSA + Trastuzumab +Capecitabine</content><footnote ID="_Ref171610144">The denominator used to calculate the rate varied from 351 to 400 in the TUKYSA arm and 173 to 197 in the control arm based on the number of patients with a baseline value and at least one post-treatment value. Grading was based on NCI-CTCAE v.4.03 for laboratory abnormalities, except for increased creatinine which only includes patients with a creatinine increase based on the upper limit of normal definition for grade 1 events (NCI CTCAE v5.0).</footnote></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Placebo + Trastuzumab +Capecitabine</content><footnoteRef IDREF="_Ref171610144"/></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Grades &#x2265;3</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Grades &#x2265;3</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Hematology</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased hemoglobin</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>59</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>51</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.5</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Chemistry</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased phosphate</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>57</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>45</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Increased bilirubin</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>47</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>30</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Increased ALT</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>46</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>27</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Increased AST</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>43</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased magnesium</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>40</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased potassium<footnote ID="_Ref171610162">Laboratory criteria for Grade 1 is identical to laboratory criteria for Grade 2.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>31</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Increased creatinine<footnote ID="_Ref171610168">Due to inhibition of renal tubular transport of creatinine without affecting glomerular function.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>33</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased sodium<footnote ID="_Ref171610174">There is no definition for Grade 2 in CTCAE v.4.03.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Increased alkaline phosphatase</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>26</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0</paragraph></td></tr></tbody></table>

<table ID="_RefID0EOABG" styleCode="Noautorules" width="100%"><caption>Table 5: Adverse Reactions (&#x2265;10%) in Patients with Unresectable or Metastatic Colorectal Cancer (MOUNTAINEER)</caption><col width="31%"/><col width="36%"/><col width="33%"/><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">TUKYSA + Trastuzumab</content></paragraph><paragraph><content styleCode="bold">N= 86</content><footnote ID="_Ref171610278">Includes 1 patient who only received trastuzumab.</footnote></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Grade 3</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td colspan="3" 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 Toprule Botrule " valign="top"><paragraph>64</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>35</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Vomiting</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</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>Abdominal pain<footnote ID="_Ref171610269">Abdominal pain includes abdominal discomfort, abdominal pain, and abdominal pain upper.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Constipation</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.2</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>44</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pyrexia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>20</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Chills</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.2</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Skin and subcutaneous disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Rash<footnote ID="_Ref171610286">Rash includes acne, dermatitis acneiform, dermatitis contact, erythema, erythema multiforme, rash, rash macular, rash maculo-papular, rash papular, rash pustular, skin exfoliation, and urticaria.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>37</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Injury, poisoning, and procedural complications</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Infusion related reaction</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="3" 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>Anemia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="3" 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>Hypertension</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7</paragraph></td></tr><tr><td colspan="3" 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>Back pain</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Arthralgia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Myalgia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Cough</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</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>Dyspnea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Anxiety</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0</paragraph></td></tr></tbody></table>