Olaparib

Olaparib is used for: Ovarian cancer, Fallopian tube cancer, Primary peritoneal cancer, Breast cancer, Pancreatic Cancer, Prostate Cancer

Oral Ovarian Cancer Recurrent ovarian cancer Indicated as maintenance treatment for recurrent ovarian cancer (including epithelial ovarian, fallopian tube or primary peritoneal cancer) in adults who are in complete or partial response to platinum-based chemotherapy 300 mg PO BID Continue until disease progression, unacceptable toxicity Advanced ovarian cancer (monotherapy) Indicated as first-line maintenance treatment for deleterious or suspected deleterious somatic or germline BRCA-mutated (gBRCAm) advanced ovarian cancer in patients who are in complete or partial response to first-line platinum-based chemotherapy 300 mg PO BID Continue until disease progression, unacceptable toxicity, or completion of 2 years of treatment Completion of 2 years of treatment Patients with complete response (no radiologic evidence): Stop treatment Patients with evidence of disease and may benefit from continuous treatment: Treat beyond 2 years Advanced ovarian cancer (combination therapy) Indicated as first-line maintenance treatment for advanced ovarian cancer in combination with bevacizumab for adults who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability Olaparib 300 mg PO BID, plus Bevacizumab 15 mg/kg IV q3Weeks for a total of 15 months (including with chemotherapy and as maintenance) Continue until disease progression, unacceptable toxicity, or completion of 2 years of treatment Refer to prescribing information for bevacizumab when used in combination with olaparib for more information Completion of 2 years of treatment Patients with complete response (no radiologic evidence): Stop treatment Patients with evidence of disease and may benefit from continuous treatment: Treat beyond 2 years Advanced ovarian cancer (after ?3 lines of chemotherapy) Indicated for treatment of adults with deleterious or suspected deleterious gBRCAm advanced ovarian cancer who have been treated with ?3 prior lines of chemotherapy 300 mg PO BID Continue treatment until disease progression or unacceptable toxicity Breast Cancer Indicated for deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer Patients who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting Patients with hormone receptor (HR)-positive breast cancer should have been treated with prior endocrine therapy or be considered inappropriate for endocrine therapy 300 mg PO BID Continue treatment until disease progression or unacceptable toxicity Pancreatic Cancer Indicated for first-line maintenance treatment of adults with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen 300 mg PO BID Continue treatment until disease progression or unacceptable toxicity Metastatic Castration-Resistant Prostate Cancer Indicated for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) in adults who have progressed following prior treatment with enzalutamide or abiraterone 300 mg PO BID Continue until disease progression or unacceptable toxicity Should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy Hepatic impairment Mild to moderate hepatic impairment (Child-Pugh Class A and B): No dosage adjustment necessary Severe hepatic impairment (Child-Pugh Class C): Not studied

Renal impairment Mild (CrCl 50-80 mL/min): No dosage adjustment necessary Moderate (CrCl 31-50 mL/min): Reduce dose to 200 mg (two 100-mg tablets) BID Severe (CrCl <30 mL/min or dialysis): Not evaluated

May be taken with or without food. Swallow whole, do not chew/crush/dissolve/divide.

Pneumonitis, including fatal cases, occurred in <1%; interrupt treatment if pneumonitis is suspected; discontinue if pneumonitis is confirmed Can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals; (see Pregnancy) Venous thromboembolic events, including pulmonary embolism, occurred in mCRPC patients who were treated with olaparib and androgen deprivation therapy; monitor for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated Myelodysplastic syndrome/ acute myeloid leukemia Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in clinical trials Monitor complete blood cell count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment Do not initiate treatment until hematological toxicity caused by previous chemotherapy (Grade ≤1) resolves

Pregnancy Based on findings in animals and mechanism of action, fetal harm may occur when administered to a pregnant woman; there are no available data on use in pregnant women to inform of drug associated risk Olaparib was teratogenic and caused embryo-fetal toxicity in rats at exposures below those in patients receiving the recommended human dose of 400 mg BID Contraception In women of childbearing potential, avoid pregnancy by using effective contraception during treatment and for at least 6 month after receiving the last dose; pregnancy testing is recommended for females of reproductive potential prior to initiating treatment Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of olaparib Advise male patients not to donate sperm during therapy and for 3 months following the last dose of olaparib Lactation No data are available regarding presence of olaparib in human milk, or on effects on breastfed infant or on milk production; because of potential for serious adverse reactions in breastfed infants from therapy, advise lactating women not to breastfeed during treatment and for 1 month after receiving last dose

May reduce efficacy of hormonal contraceptives. May decrease serum concentration with moderate or severe CYP3A4 inducers. May increase serum concentration with moderate or strong CYP3A4 inhibitors. Increased myelosuppression with other antineoplastic agents.

Side effects of Olaparib : >10% (Maintenance Treatment for BRCA-mutated Advanced Ovarian) Decreased hemoglobin (87%) Increased mean corpuscular volume (87%) Nausea (77%) Decrease leukocytes (70%) Fatigue (67%) Decreased lymphocytes (67%) Decreased ANC (51%) Abdominal pain (45%) Vomiting (40%) Anemia (38%) Diarrhea (37%) Decreased platelets (35%) Increased serum creatinine (34%) Constipation (28%) Upper respiratory tract infection (eg, influenza, nasopharyngitis, bronchitis) (28%) Dysgeusia (26%) Anemia, Grade 3 or 4 (21%) Dizziness (20%) Decreased appetite (20%) Decreased hemoglobin, Grade 3 or 4 (19%) Neutropenia (17%) Dyspepsia (17%) Dyspnea (15%) Decreased lymphocytes, Grade 3 or 4 (14%) Urinary tract infection (13%) Thrombocytopenia (11%) Stomatitis (11%) >10% (Maintenance Treatment for Recurrent Advanced Ovarian) Increased mean corpuscular volume (89%) Decreased hemoglobin (83%) Nausea (76%) Decreased leukocytes (69%) Decreased lymphocytes (67%) Fatigue (66%) Decreased ANC (51%) Anemia (44%) Increased serum creatinine (44%) Decreased platelets (42%) Vomiting (37%) Upper respiratory tract infection (36%) Diarrhea (33%) Arthralgia/myalgia (30%) Dysgeusia (27%) Headache (26%) Decreased appetite (22%) Stomatitis (20%) Neutropenia (19%) Cough (18%) Leukopenia (16%) Hypomagnesemia (14%) Thrombocytopenia (14%) Dizziness (13%) Dyspepsia (11%) Increased creatinine (11%) 1-10% (BRCA-mutated Advanced Ovarian) Maintenance treatment Neutropenia, Grade 3 or 4 (6%) Fatigue, Grade 3 or 4 (4%) Leukopenia, Grade 3 or 4 (3%) Diarrhea, Grade 3 or 4 (3%) Abdominal pain, Grade 3 or 4 (2%) Thrombocytopenia, Grade 3 or 4 (1%) Nausea, Grade 3 or 4 (1%) 1-10% (Maintenance Treatment for Recurrent Advanced Ovarian) Edema (8%) Rash (6%) Fatigue, Grade 3 or 4 (4%) Nausea, Grade 3 or 4 (3%) Vomiting, Grade 3 or 4 (3%) Diarrhea, Grade 3 or 4 (2%) Lymphopenia (1%) Headache, Grade 3 or 4 (1%) Stomatitis, Grade 3 or 4 (1%)

Inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3 PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair