b'LYNPARZA (olaparib) tablets, for oral use 2In the pooled safety population, 56% of patients were exposed for 6 months or longer and 28%Treatment of BRCA-mutated Metastatic Castration-Resistant Prostate Cancer in Combination were exposed for greater than one year in the Lynparza group. with Abiraterone and Prednisone or PrednisoloneIn this pooled safety population, the most common adverse reactions in 10% of patients werePROpelnausea (60%), fatigue (55%), anemia (36%), vomiting (32%), diarrhea (24%), decreased appetiteThe safety of Lynparza in combination with abiraterone and prednisone or prednisolone for the (22%), headache (16%), dysgeusia (15%), cough (15%), neutropenia (14%), dyspnea (14%),treatment of patients in the rst-line mCRPC setting was investigated in PROpel [see Clinical dizziness (12%), dyspepsia (12%), leukopenia (11%), and thrombocytopenia (10%). Studies (14.8) in the full Prescribing Information]. Patients were randomized to receive either HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer Lynparza tablets 300 mg orally twice daily plus abiraterone tablets 1000 mg once daily (Lynparza/ PROfound abiraterone) (n=398), or placebo plus abiraterone 1000 mg once daily (placebo/abiraterone) The safety of Lynparza as monotherapy was evaluated in patients with mCRPC and HRR gene(n=396) until disease progression or unacceptable toxicity. Patients in both arms also received mutations who have progressed following prior treatment with enzalutamide or abiraterone ineither prednisone or prednisolone 5 mg twice daily.PROfound [see Clinical Studies (14.7) in the full Prescribing Information]. This study was aFatal adverse reactions occurred in 6% of patients, including COVID-19 (3%) and pneumonias randomized, open-label, multi-center study in which 386 patients received either Lynparza tablets(0.5%). 300 mg orally twice daily (n=256) or investigators choice of enzalutamide or abiraterone acetateSerious adverse reactions occurred in 39% of patients. Serious adverse reactions reported in (n=130) until disease progression or unacceptable toxicity. Among patients receiving Lynparza, 2% of patients included anemia (6%), COVID-19 (6%), pneumonia (4.5%), pulmonary embolism 62% were exposed for 6 months or longer and 20% were exposed for greater than one year. (3.5%), and urinary tract infection (3%).Fatal adverse reactions occurred in 4% of patients treated with Lynparza. These includedPermanent discontinuation of Lynparza due to adverse reactions occurred in 16% of patients pneumonia (1.2%), cardiopulmonary failure (0.4%), aspiration pneumonia (0.4%), intestinaltreated in the Lynparza with abiraterone arm. The most common adverse reactions which resulted diverticulum (0.4%), septic shock (0.4%), Budd-Chiari Syndrome (0.4%), sudden death (0.4%),in permanent discontinuation of Lynparza were anemia (4.3%) and pneumonia (1.5%).and acute cardiac failure (0.4%). Dosage interruption of Lynparza due to adverse reactions occurred in 48% of patients treated Serious adverse reactions occurred in 36% of patients receiving Lynparza. The most frequentin the Lynparza with abiraterone arm. The most common (2%) adverse reactions requiring serious adverse reactions (2%) were anemia (9%), pneumonia (4%), pulmonary embolism (2%),dosage interruption of Lynparza were anemia (16%), COVID-19 (6%) fatigue (3.5%), nausea fatigue/asthenia (2%), and urinary tract infection (2%). (2.8%), pulmonary embolism (2.3%), and diarrhea (2.3%). Dose interruptions due to an adverse reaction of any grade occurred in 45% of patients receivingDose reduction of Lynparza due to adverse reactions occurred in 21% of patients treated in Lynparza; dose reductions due to an adverse reaction occurred in 22% of Lynparza patients. Thethe Lynparza with abiraterone arm. The most common (2%) adverse reactions requiring most frequent adverse reactions leading to dose interruption of Lynparza were anemia (25%) anddosage reductions of Lynparza were anemia (11%) and fatigue (2.5%).thrombocytopenia (6%) and the most frequent adverse reaction leading to reduction of LynparzaThe most common adverse reactions (10%) in patients who received Lynparza/abiraterone was anemia (16%). Discontinuation due to adverse reactions occurred in 18% of Lynparza. Thewere anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), adverse reaction that most frequently led to discontinuation of Lynparza was anemia (7%). lymphopenia (14%), abdominal pain (13%), and dizziness (14%). Tables 14 and 15 summarize the adverse reactions and laboratory abnormalities, respectively,Tables16and17summarizeadversereactionsandlaboratoryabnormalitiesinPROpel,in patients in PROfound. respectively.Table 14Adverse Reactions *Reported in 10% of Patients in PROfoundAdverse Reactions Lynparza tablets Enzalutamide or Table 16 Adverse Reactions (10%) in Patients Who Received Lynparza (with a Difference n=256 abirateroneof 5% Compared to Placebo) in PROpeln=130 Adverse Reactions* Lynparza/abirateronePlacebo/abiraterone Grades 1-4 Grades 3-4 Grades 1-4 Grades 3-4 n=398 n=396(%) (%) (%) (%) Grades 1-4 Grades 3-4 Grades 1-4 Grades 3-4Blood and lymphatic disorders (%) (%) (%) (%)Anemia46 21 15 5 Blood and Lymphatic DisordersThrombocytopenia12 4 3 0 Anemia48 16 18 3.3Gastrointestinal disorders Lymphopenia14 5 6 1.8Nausea 41 1 19 0 General Disorders and Administration Site ConditionsDiarrhea 21 1 7 0 Fatigue (including38 2.3 30 1.5Vomiting 18 2 12 1 asthenia)General disorders and Gastrointestinal Disordersadministration site conditions Nausea 30 0.3 14 0.3Fatigue (including asthenia) 41 3 32 5 Diarrhea 19 1 10 0.3Metabolism and nutrition disorders Abdominal pain13 0 7 0.5Decreased appetite30 1 18 1 Metabolism and nutrition disordersRespiratory, thoracic, and mediastinal disorders Decreased appetite 16 1 7 0Cough 11 0 2 0 Nervous System DisordersDyspnea 10 2 3 0 Dizziness14 0.3 7 0*Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. *Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Includes anemia and hemoglobin decreased. (NCI CTCAE), version4.03. Includes platelet count decreased and thrombocytopenia. Includes anemia, anemia macrocytic, and red blood cell count decreased Includes lymphocyte count decreased and lymphopeniaClinically relevant adverse reactions that occurred in 10% of patients receiving Lynparza were Includes abdominal discomfort, abdominal pain, abdominal pain upper, and abdominal pain lowerneutropenia (9%), VTE (7%), dizziness (7%), dysgeusia (7%), dyspepsia (7%), headache (6%), Includes dizziness and vertigo.pneumonia (5%), stomatitis (5%), rash (4%), blood creatinine increase (4%), pneumonitis (2%),Clinically relevant adverse reactions that occurred in 10% for patients receiving Lynparza plus upper abdominal pain (2%), and hypersensitivity (1%). abiraterone were headache (9%), VTE (8%), rash (7%), dysgeusia (6%), acute kidney injury (3%), Table 15Laboratory Abnormalities Reported in 25% of Patients in PROfound and stomatitis (2.5%). Lynparza tablets Enzalutamide orTable 17 Selected Laboratory Abnormalities Reported in 20% of Patients in PROpeln= 256 abiraterone Laboratory Parameter * n=130 Laboratory Parameter Lynparza/abirateronePlacebo/abirateroneGrades 1-4 Grades 3-4 Grades 1-4 Grades 3-4 n=398* n=396*(%) (%) (%) (%) Grades 1-4 Grades 3-4 Grades 1-4 Grades 3-4Decrease in hemoglobin98 13 73 4 (%) (%) (%) (%)Decrease in lymphocytes62 23 34 13 Decrease in hemoglobin 97 12 81 1.3Decrease in leukocytes 53 4 21 0 Decrease in lymphocytes 70 23 49 11Decrease in absolute 34 3 9 0 Decrease in platelets23 1.2 20 0.3neutrophil count Decrease in absolute 23 5 6 0*Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1. neutrophil countThis number represents the safety population. The derived values in the table are based on the total number of*This number represents the safety population. The derived values in the table are based on the total numberevaluable patients for each laboratory parameter. of evaluable patients for each laboratory parameter.'