780P - Propensity-score matching analysis for efficacy of platinum-based versus non-platinum chemotherapy in patients with “platinum-resistant” ovarian cancer (PROC): Real-world recent cohort study

Background

PROC patients with platinum-free interval (PFI) <6 mo. are often considered platinum-resistant and should be treated with non-platinum based chemotherapy. However, this was never confirmed in properly conducted randomized trials. We conducted a retrospective trial with propensity score matching to assess efficacy of platinum rechallenge in PROC patients.

Methods

408 patients with PROC (PFI≤180 days) who received platinum-based or non-platinum-based chemotherapy for 1^st or 2^nd relapse of high-grade serous or endometrioid ovarian carcinoma were identified from the institutional database (2014-2023). Propensity-score matching with 1:1 ratio was used to adjust the cohorts for potential biases and intrinsic imbalances (ECOG 0-1 vs 2, 1^st vs 2^nd number of relapse, BRCA mutated vs “wild-type”/unknown, prescribed non-platinum agent, PFI, use of bevacizumab). Patients with poor performance status (ECOG3-4) or those who received previous PARP-inhibitors were excluded. Progression-free survival (PFS) and overall survival (OS) were compared using Kaplan-Meier analysis. Response rates (RR) to therapy were assessed with GCIG criteria.

Results

246 matched patients were enrolled in the study (median age 58 years, median PFI 3.9 mo., 23% - BRCAmut/HRD+, 67% patients treated for 1st relapse) with 123 patients allocated to each arm. RR for patients treated with platinum-based and non-platinum based chemotherapy was 52% and 15% (p<0.001), respectively, and disease control rate (PR+CR+SD) was 72% and 42% (p<0.001). Median PFS was 7.43 months (95% confidence interval [CI], 6.77 to 8.23) in the platinum arm and 3.17 months (95% CI, 2.77 to 4.03) in the non-platinum arm (hazard ratio for progression, 0.45; 95% CI, 0.35 to 0.59; p < 0.001). Longer PFI (p<0.001), BRCA/HRD-positive disease (p=0.009), taxanes (p=0.026) and treatment with bevacizumab (p=0.002) were associated with improved PFS in Cox regression analysis.

Conclusions

the concept of PROC should be further reassessed in further randomized trials, as many patients may benefit from platinum rechallenge in this setting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Rumyantsev: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BIOCAD, Merck, MSD, Roche; Financial Interests, Personal, Local PI: AstraZeneca. I. Pokataev: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. A. Tyulyandina: Financial Interests, Personal, Advisory Board: Astra-Zeneca, MSD, Biocad, Pfizer; Financial Interests, Personal, Invited Speaker: Eisai, Roche; Non-Financial Interests, Advisory Role: MSD; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca, MSD, Biocad. S. Tjulandin: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, BioCad, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, R-Pharm, Pierre Fabre; Financial Interests, Personal, Ownership Interest: RusPharmTech; Financial Interests, Personal and Institutional, Local PI: Merck Sharp Dohme, Eisai, AbbVie, Novartis, Bristol Myers Squibb; Financial Interests, Personal, Coordinating PI: Servier; Non-Financial Interests, Member: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Leadership Role: Russian Society of Clinical Oncology (RUSSCO); Other, The Chair: Russian Society of Clinical Oncology (RUSSCO). All other authors have declared no conflicts of interest.