Platinum Rechallenge in Platinum-Resistant Ovarian Cancer: Clinical Outcomes and the Impact of BRCA Status

Objective: To evaluate the clinical benefit of platinum rechallenge in patients with platinum-resistant ovarian cancer (PROC) and to explore the predictive role of BRCA mutation status. Methods: We retrospectively evaluated platinum rechallenge in PROC at Vall d'Hebron University Hospital between 2010 and 2023. Eligibility required ≥1 prior non-platinum regimen and ≥12 months since the last platinum dose. Objective response rate (ORR) per RECIST 1.1 and survival outcomes were analyzed by BRCA status and prior treatment lines. Results: ORR was 57% (95%CI, 42.1-73.0%) in the overall cohort (n = 63), 77% in BRCA-mutated patients (n = 13), and 50% in BRCA wild-type patients (n = 46). Median progression-free survival (PFS) was 7.3 months overall, which was longer in BRCA-mutated versus BRCA wild-type patients (8.4 vs. 7.4 months; HR 0.47, 95%CI 0.23-0.94; p = 0.033). An exploratory subgroup analysis suggested longer PFS among BRCA-mutated patients with ≤4 prior lines; however, this small subgroup finding should be considered hypothesis-generating. A platinum-free interval >6 months after rechallenging was observed in 38.5% of BRCA-mutated versus 13% of BRCA wild-type patients. Conclusions: Platinum rechallenge showed clinically meaningful activity in selected patients with PROC after an extended interval of intervening non-platinum therapy. These findings support the concept that platinum sensitivity may be dynamic and suggest that BRCA status and clinical selection factors may help inform individualized treatment sequencing in the post-PARP inhibitor era. Prospective validation with broader molecular characterization is warranted.