Overall survival with maintenance olaparib in platinum-sensitive relapsed ovarian cancer by somatic or germline BRCA and homologous recombination repair mutation status

Br J Cancer. 2025 May;132(8):725-732. doi: 10.1038/s41416-025-02966-x. Epub 2025 Mar 17.

Abstract

Background: The open-label, single-arm, multicentre ORZORA trial (NCT02476968) evaluated maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) with a germline (g) or somatic (s) BRCA1 and/or BRCA2 mutation (BRCAm) or a non-BRCA homologous recombination repair mutation (non-BRCA HRRm).

Methods: Patients were in response to platinum-based chemotherapy after ≥2 prior lines of treatment and underwent prospective central screening for tumour BRCA status, then central gBRCAm testing to determine sBRCAm or gBRCAm status. An exploratory cohort evaluated non-BRCA HRRm in 13 predefined genes. Patients received olaparib 400 mg (capsules) twice daily until investigator-assessed disease progression. Secondary endpoints included overall survival (OS) and safety.

Results: 177 patients received olaparib. At the final data cutoff (25 June 2021), median OS from study enrolment was 46.8 (95% confidence interval [CI] 37.9-54.4), 43.2 (31.7-NC [not calculated]), 47.4 (37.9-NC) and 44.9 (28.9-NC) months in the BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts, respectively. No new safety signals were identified.

Conclusion: Maintenance olaparib showed consistent clinical activity in the BRCAm and sBRCAm cohorts; exploratory analysis suggested similar activity in the non-BRCA HRRm cohort. These findings highlight that patients with PSR OC, beyond those with gBRCAm, may benefit from maintenance olaparib.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein* / genetics
  • BRCA2 Protein* / genetics
  • Female
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local* / drug therapy
  • Neoplasm Recurrence, Local* / genetics
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / mortality
  • Ovarian Neoplasms* / pathology
  • Phthalazines* / administration & dosage
  • Phthalazines* / adverse effects
  • Phthalazines* / therapeutic use
  • Piperazines* / administration & dosage
  • Piperazines* / adverse effects
  • Piperazines* / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors* / administration & dosage
  • Poly(ADP-ribose) Polymerase Inhibitors* / therapeutic use
  • Recombinational DNA Repair / genetics

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • olaparib
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors