Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy

Susan M. Domchek, Carol Aghajanian, Ronnie Shapira-Frommer, Rita K. Schmutzler, M. William Audeh, Michael Friedlander, Judith Balmaña, Gillian Mitchell, Georgeta Fried, Salomon M. Stemmer, Ayala Hubert, Ora Rosengarten, Niklas Loman, Jane D. Robertson, Helen Mann, Bella Kaufman

Research output: Contribution to journalArticlepeer-review

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.gov NCT01078662) have been reported previously. Methods Eligible patients were treated with oral olaparib 400 mg 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: 8.2 months (95% CI 5.6-13.5) compared with 8.0 months (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. Conclusion Following ≥ 3 prior lines of chemotherapy, olaparib 400 mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified.

Original languageEnglish
Pages (from-to)199-203
Number of pages5
JournalGynecologic Oncology
Volume140
Issue number2
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • BRCA1/2 mutation
  • Olaparib
  • Ovarian cancer
  • Phase II

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