5566 Background: Platinum-resistant ovarian cancer (PROC), defined as recurrence within 6 months of completing platinum-based chemotherapy, has limited treatment options and poor outcomes. Although guidelines recommend non-platinum therapy, platinum rechallenge still occurs in real-world practice, despite limited evidence. This study examines real-world patterns and outcomes of platinum rechallenge versus non-platinum therapy at first PROC occurrence overall and by biomarker status, prior therapy, and time to PROC. Methods: Using the US-based, EHR-derived deidentified Flatiron Health Research Database, ovarian cancer patients diagnosed after January 1, 2017 (data cutoff August 31, 2025) were selected. Patients with PROC, defined as progressing ≤ 6 months after platinum, that received subsequent therapy were included; primary platinum refractory patients (< 3 months) were excluded. Patients were grouped by first PROC therapy (platinum rechallenge vs non-platinum therapy), and rwPFS and rwOS were assessed overall and by BRCA/HRD status, use of prior first-line maintenance (1LM), number of prior platinum lines, and time to PROC. Associations were assessed using Kaplan-Meier estimates and IPTW-adjusted Cox models accounting for demographics, ECOG PS, practice type, insurance, index year, biomarkers, and prior 1LM and platinum exposure. Results: Among 29,194 patients with ovarian cancer, 2,907 had PROC. Of these, 528 received platinum rechallenge and 2,379 received non-platinum therapy (71% received chemotherapy ± bevacizumab) as subsequent treatment. Baseline characteristics in both groups were similar; the platinum rechallenge group had fewer patients with BRCA mutations (BRCAm) (9.3% vs 12%) and no residual disease (36% vs 40%) but more with only one prior platinum line (56% vs 48%). Median rwPFS was 5.8 mo with platinum rechallenge vs 3.9 mo with non-platinum therapy (adjusted HR 0.72, 95% CI, 0.64 to 0.81; P < .001), and median rwOS was 13 vs 11 mo (adjusted HR 0.81, 95% CI, 0.72 to 0.92; P = .001). In adjusted analyses, rwPFS advantage of platinum rechallenge was consistent across major subgroups, including biomarker-defined populations (BRCA-wild type and HRD-positive non-BRCAm), prior 1LM and platinum exposure, and time to PROC. rwOS benefit was more limited, confined to patients with BRCAm, earlier recurrence, and more heavily pretreated disease, with limited events in several subgroups. Conclusions: In this large real-world cohort, platinum rechallenge improved rwPFS and rwOS vs non-platinum therapy in PROC. Consistent rwPFS benefits across most subgroups and selective rwOS advantages, particularly in BRCAm, highlight heterogeneity within PROC populations and support individualized decisions for platinum rechallenge beyond a strict 6-month platinum-free interval. Prospective studies are required to identify patients most likely to benefit from platinum rechallenge.
Yerram et al. (Wed,) studied this question.