title: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer.
abstract: BACKGROUND
  Olaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that has shown antitumor activity in patients with high-grade serous ovarian cancer with or without BRCA1 or BRCA2 germline mutations.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled, phase 2 study to evaluate maintenance treatment with olaparib in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had received two or more platinum-based regimens and had had a partial or complete response to their most recent platinum-based regimen. Patients were randomly assigned to receive olaparib, at a dose of 400 mg twice daily, or placebo. The primary end point was progression-free survival according to the Response Evaluation Criteria in Solid Tumors guidelines.
  
  
  RESULTS
  Of 265 patients who underwent randomization, 136 were assigned to the olaparib group and 129 to the placebo group. Progression-free survival was significantly longer with olaparib than with placebo (median, 8.4 months vs. 4.8 months from randomization on completion of chemotherapy; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.25 to 0.49; P<0.001). Subgroup analyses of progression-free survival showed that, regardless of subgroup, patients in the olaparib group had a lower risk of progression. Adverse events more commonly reported in the olaparib group than in the placebo group (by more than 10% of patients) were nausea (68% vs. 35%), fatigue (49% vs. 38%), vomiting (32% vs. 14%), and anemia (17% vs. 5%); the majority of adverse events were grade 1 or 2. An interim analysis of overall survival (38% maturity, meaning that 38% of the patients had died) showed no significant difference between groups (hazard ratio with olaparib, 0.94; 95% CI, 0.63 to 1.39; P=0.75).
  
  
  CONCLUSIONS
  Olaparib as maintenance treatment significantly improved progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. Interim analysis showed no overall survival benefit. The toxicity profile of olaparib in this population was consistent with that in previous studies. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT00753545.).
authors.affiliation: University College London (UCL) Cancer Institute, UCL & UCL Hospitals Comprehensive Biomedical Research Centre, 90 Tottenham Court Rd., London W1T 4TJ, United Kingdom. j.ledermann@ctc.ucl.ac.uk
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ledermann
authors.forename: Philipp
authors.initials: P
authors.lastname: Harter
authors.forename: Charlie
authors.initials: C
authors.lastname: Gourley
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Gordon
authors.initials: G
authors.lastname: Rustin
authors.forename: Clare
authors.initials: C
authors.lastname: Scott
authors.forename: Werner
authors.initials: W
authors.lastname: Meier
authors.forename: Ronnie
authors.initials: R
authors.lastname: Shapira-Frommer
authors.forename: Tamar
authors.initials: T
authors.lastname: Safra
authors.forename: Daniela
authors.initials: D
authors.lastname: Matei
authors.forename: Euan
authors.initials: E
authors.lastname: Macpherson
authors.forename: Claire
authors.initials: C
authors.lastname: Watkins
authors.forename: James
authors.initials: J
authors.lastname: Carmichael
authors.forename: Ursula
authors.initials: U
authors.lastname: Matulonis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D053208:Kaplan-Meier Estimate; D060046:Maintenance Chemotherapy; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010793:Phthalazines / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010793:Phthalazines; D010879:Piperazines; C531550:olaparib