Maintenance olaparib monotherapy in patients with platinum-sensitive relapsed ovarian cancer without a germline BRCA1 and/or BRCA2 mutation: Final overall survival results from the OPINION trial

Gynecol Oncol. 2025 Jun:197:74-82. doi: 10.1016/j.ygyno.2025.04.580. Epub 2025 Apr 28.

Abstract

Objective: Maintenance olaparib demonstrated clinical activity for progression-free survival in patients without a germline BRCA1 and/or BRCA2 mutation (non-gBRCAm) who had platinum-sensitive relapsed ovarian cancer in the phase IIIb, open-label, single-arm, non-comparator, international OPINION trial (NCT03402841). We report final overall survival (OS; secondary endpoint), prespecified secondary endpoint updates and ad hoc OS analysis by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status.

Methods: Patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, ≥2 prior lines of platinum-based chemotherapy, and in response following their last platinum-based chemotherapy received 300 mg olaparib tablets twice daily until disease progression or unacceptable toxicity.

Results: 279 patients were enrolled and treated. With a median follow-up in patients censored for OS of 33.1 months (data cut-off September 17, 2021), median OS was 32.7 months (95 % CI 29.5-35.3); the 24-month OS rate was 65.8 %. In ad hoc subgroup analyses, OS rates tended to be higher in patients with HRD-positive tumors; 24-month OS rates were 81.5 %, 74.2 %, 72.0 % and 55.8 % in the sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative subgroups, respectively. Grade ≥ 3 treatment-emergent adverse events were reported in 82 patients (29.4 %), most commonly anemia (13.6 %). Overall, two cases of myelodysplastic syndrome were reported (no new cases since the primary analysis).

Conclusion: These data provide additional evidence of olaparib as maintenance therapy in patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, with longer OS observed in those with HRD-positive tumors. The safety profile was consistent with the primary analysis and known safety profile of olaparib, with no new safety findings.

Keywords: BRCA; Maintenance; Olaparib; Ovarian cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Carcinoma, Ovarian Epithelial* / drug therapy
  • Carcinoma, Ovarian Epithelial* / genetics
  • Carcinoma, Ovarian Epithelial* / mortality
  • Female
  • Germ-Line Mutation
  • Humans
  • Maintenance Chemotherapy
  • Middle Aged
  • Neoplasm Recurrence, Local* / drug therapy
  • Neoplasm Recurrence, Local* / genetics
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / mortality
  • 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* / adverse effects
  • Poly(ADP-ribose) Polymerase Inhibitors* / therapeutic use
  • Progression-Free Survival

Substances

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