title: FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy.
abstract: On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland. Geoffrey.Kim@fda.hhs.gov.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kim
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gwynn
authors.initials: G
authors.lastname: Ison
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Amy E
authors.initials: AE
authors.lastname: McKee
authors.affiliation: Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Tang
authors.affiliation: Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gwise
authors.affiliation: Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.affiliation: Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Eunice
authors.initials: E
authors.lastname: Lee
authors.affiliation: Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Abraham
authors.initials: A
authors.lastname: Tzou
authors.affiliation: Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Reena
authors.initials: R
authors.lastname: Philip
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Haw-Jyh
authors.initials: HJ
authors.lastname: Chiu
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Tiffany K
authors.initials: TK
authors.lastname: Ricks
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Todd
authors.initials: T
authors.lastname: Palmby
authors.affiliation: New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Russell
authors.affiliation: New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Ladouceur
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Elimika
authors.initials: E
authors.lastname: Pfuma
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Li
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Venugopal
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Amna
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010793:Phthalazines / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531550:olaparib