Olaparib as Treatment Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer: Phase III SOLO3 Study Final Overall Survival Results

J Clin Oncol. 2025 Apr 20;43(12):1408-1416. doi: 10.1200/JCO.24.00933. Epub 2024 Dec 12.

Abstract

Olaparib treatment significantly improved objective response rate (primary end point) and progression-free survival versus nonplatinum chemotherapy in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer in the open-label phase III SOLO3 trial (ClinicalTrials.gov identifier: NCT02282020). We report final overall survival (OS; prespecified secondary end point), post hoc OS analysis by number of previous chemotherapy lines, and exploratory BRCA reversion mutation analysis. Two hundred sixty-six patients were randomly assigned 2:1 to olaparib tablets (300 mg twice daily; n = 178) or physician's choice of single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan; n = 88). OS was similar with olaparib versus chemotherapy (hazard ratio [HR], 1.07 [95% CI, 0.76 to 1.49]; P = .71, median 34.9 and 32.9 months, respectively, full analysis set). OS with olaparib was favorable in patients with two previous chemotherapy lines (HR, 0.83 [olaparib v chemotherapy] [95% CI, 0.51 to 1.38]; median 37.9 v 28.8 months); however, a potential detrimental effect was seen in patients with at least three previous chemotherapy lines (HR, 1.33 [95% CI, 0.84 to 2.18]; median 29.9 v 39.4 months). BRCA reversion mutations might have contributed to this finding. No patient randomly assigned to olaparib with a BRCA reversion mutation detected at baseline (6 of 170 [3.5%]) achieved an objective tumor response.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Female
  • Gemcitabine
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local* / drug therapy
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / mortality
  • Ovarian Neoplasms* / pathology
  • Paclitaxel / administration & dosage
  • Phthalazines* / administration & dosage
  • Phthalazines* / adverse effects
  • Phthalazines* / therapeutic use
  • Piperazines* / administration & dosage
  • Piperazines* / adverse effects
  • Piperazines* / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors* / adverse effects
  • Poly(ADP-ribose) Polymerase Inhibitors* / therapeutic use
  • Polyethylene Glycols / administration & dosage
  • Progression-Free Survival
  • Topotecan / administration & dosage

Substances

  • olaparib
  • Phthalazines
  • Piperazines
  • Paclitaxel
  • Doxorubicin
  • liposomal doxorubicin
  • Topotecan
  • Deoxycytidine
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Gemcitabine
  • Polyethylene Glycols
  • BRCA1 Protein
  • BRCA2 Protein
  • BRCA1 protein, human
  • BRCA2 protein, human

Associated data

  • ClinicalTrials.gov/NCT02282020