title: Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety.
abstract: The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy.
  
  
  
  This analysis evaluated pooled data from two phase I trials [NCT00516373 (study 2); NCT00777582 (study 24)] and four phase II trials [NCT00494442 (study 9); NCT00628251 (study 12); NCT00679783 (study 20); NCT01078662 (study 42)] that recruited women with relapsed ovarian, fallopian tube or peritoneal cancer. All patients had a documented gBRCAm and were receiving olaparib 400 mg monotherapy twice daily (capsule formulation) at the time of relapse. Objective response rate (ORR) and duration of response (DoR) were evaluated using original patient outcomes data for patients with measurable disease at baseline.
  
  
  
  Of the 300 patients in the pooled population, 273 had measurable disease at baseline, of whom 205 (75%) had received ≥3 lines of prior chemotherapy. In the pooled population, the ORR was 36% [95% confidence interval (CI) 30-42] and the median DoR was 7.4 months (95% CI 5.7-9.1). The ORR among patients who had received ≥3 lines of prior chemotherapy was 31% (95% CI 25-38), with a DoR of 7.8 months (95% CI 5.6-9.5). The safety profile of olaparib was similar in patients who had received ≥3 lines of prior chemotherapy compared with the pooled population; grade ≥3 adverse events were reported in 54% and 50% of patients, respectively.
  
  
  
  Durable responses to olaparib were observed in patients with relapsed gBRCAm ovarian cancer who had received ≥3 lines of prior chemotherapy.
  
  
  
  NCT00516373; NCT00494442; NCT00628251; NCT00679783; NCT00777582; NCT01078662.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston. Electronic address: ursula_matulonis@dfci.harvard.edu.
authors.forename: U A
authors.initials: UA
authors.lastname: Matulonis
authors.affiliation: Department of Hematology/Oncology, Massachusetts General Hospital, Boston.
authors.forename: R T
authors.initials: RT
authors.lastname: Penson
authors.affiliation: Department of Medicine, Basser Research Center and Abramson Cancer Center, Philadelphia, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Domchek
authors.affiliation: Division of Oncology, Sheba Medical Center, Tel HaShomer, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Kaufman
authors.affiliation: Division of Oncology, Sheba Medical Center, Tel HaShomer, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Shapira-Frommer
authors.affiliation: Division of Medical Oncology, Cedars-Sinai Medical Center, Los Angeles, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Audeh
authors.affiliation: Drug Development Unit, Royal Marsden Hospital and Institute of Cancer Research, Sutton, UK.
authors.forename: S
authors.initials: S
authors.lastname: Kaye
authors.affiliation: Drug Development Unit, Royal Marsden Hospital and Institute of Cancer Research, Sutton, UK.
authors.forename: L R
authors.initials: LR
authors.lastname: Molife
authors.affiliation: Department of Medical Oncology, BC Cancer Agency, Vancouver, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Gelmon
authors.affiliation: Global Medicines Development, AstraZeneca, Macclesfield, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Robertson
authors.affiliation: Global Medicines Development, AstraZeneca, Macclesfield, UK.
authors.forename: H
authors.initials: H
authors.lastname: Mann
authors.affiliation: Global Medicines Development, AstraZeneca, Wilmington.
authors.forename: T W
authors.initials: TW
authors.lastname: Ho
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Coleman
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010793:Phthalazines / Q000008:administration & dosage* / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531550:olaparib
keywords: BRCA1/2 mutation; monotherapy; olaparib; ovarian cancer; pooled analysis