Response to subsequent platinum-based chemotherapy post PARP inhibitor in recurrent epithelial ovarian cancer.

Abstract

5578 Background: Maintenance therapy with PARP inhibitors (PARPi) can increase progression free survival (PFS) for recurrent or metastatic platinum-sensitive epithelial ovarian cancer (EOC). Little is known about disease trajectory following treatment with these agents, though some evidence suggests a decreased response to subsequent platinum-based chemotherapy. This retrospective cohort study assessed real-world response rates to platinum-based chemotherapy for recurrent high grade EOC following treatment with a PARPi. Methods: All patients prescribed a PARPi as maintenance therapy for recurrent or metastatic EOC at the Ottawa Regional Cancer Center (ORCC) from September 2017 to May 2022 were included. PFS following penultimate therapy (line of therapy preceding PARPi initiation) as well as the PFS following subsequent platinum-based chemotherapy in patients with disease progression more than 6 months after penultimate therapy were calculated. Incidence of platinum resistance in patients with disease progression following PARPi therapy was determined. Results: 91 patients were included in the analysis including 54 patients on niraparib and 36 patients on olaparib. Follow-up after initiation of PARPi ranged from 4.6 months to 62.0 months with a median of 16.3 months. 54 (59.3%) of patients experienced disease progression after initiation of PARPi therapy, including 10 (11.0%) who progressed within 6 months of their penultimate therapy. Of the 44 patients who experienced disease progression more than 6 months following penultimate therapy, 32 (72.7%) were rechallenged with platinum-based chemotherapy. Of these, 16 (50.0%) experienced further disease progression with 14 (43.8%) progressing within 6 months of their platinum rechallenge. Median PFS following platinum rechallenge was 4.4 months (from 0.8 months to 34.9 months), significantly lower than previous reports. Conclusions: Patients who experienced disease progression following PARPi therapy showed a poor response to subsequent platinum-based chemotherapy, even when progression occurred more than 6 months after completion of their penultimate platinum-based chemotherapy. This supports the theory that PARPi resistance may be a surrogate for platinum resistance and raises concern for possible contribution of PARPi in the induction of platinum resistance in recurrent EOC.