title: Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy.
abstract: OBJECTIVE
  The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.govNCT01078662) have been reported previously.
  
  
  METHODS
  Eligible patients were treated with oral olaparib 400mg bid capsule monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for patients with measurable disease at baseline. Safety and tolerability were assessed for all patients by adverse event (AE) incidence and changes in laboratory parameters. Platinum resistance status was obtained retrospectively, and responses to olaparib evaluated.
  
  
  RESULTS
  In patients with gBRCA1/2m ovarian cancer, 154/193 (80%) had received ≥3 prior lines of chemotherapy, of whom 137/154 (89%) had measurable disease at baseline. ORR was 34% (46/137; 95% confidence interval [CI] 26-42) and median DoR was 7.9 (95% CI 5.6-9.6) months. ORR in platinum-resistant tumors was 30%. Median DoR for platinum-sensitive and platinum-resistant disease was similar: 8.2months (95% CI 5.6-13.5) compared with 8.0months (4.8-14.8), respectively. Six of the 193 (3%) patients had an AE with an outcome of death. None of these AEs at time of occurrence was considered causally related to olaparib.
  
  
  CONCLUSIONS
  Following ≥3 prior lines of chemotherapy, olaparib 400mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified.
authors.affiliation: Basser Research Center and Abramson Cancer Center, Philadelphia, PA, USA. Electronic address: susan.domchek@uphs.upenn.edu.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
authors.affiliation: Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Shapira-Frommer
authors.affiliation: Center for Familial Breast and Ovarian Cancer and Center of Integrated Oncology, Cologne, Germany.
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.affiliation: Samuel Oschin Cancer Institute, Los Angeles, CA, USA.
authors.forename: M William
authors.initials: MW
authors.lastname: Audeh
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.affiliation: Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Balmaña
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
authors.forename: Gillian
authors.initials: G
authors.lastname: Mitchell
authors.affiliation: Institute of Oncology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Georgeta
authors.initials: G
authors.lastname: Fried
authors.affiliation: Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
authors.affiliation: Hadassah-Hebrew University Hospital Sharett Institute of Oncology, Jerusalem, Israel; Sharett Institute of Oncology, Jerusalem, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Hubert
authors.affiliation: Shaare Zedek Medical Centre, Jerusalem, Israel.
authors.forename: Ora
authors.initials: O
authors.lastname: Rosengarten
authors.affiliation: Skånes universitetssjuk Lund, Lund, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Loman
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Jane D
authors.initials: JD
authors.lastname: Robertson
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Mann
authors.affiliation: Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Kaufman
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010793:Phthalazines / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531550:olaparib
keywords: BRCA1/2 mutation; Olaparib; Ovarian cancer; Phase II