Abstract

PARP inhibitors (PARPi) have shown have activity in the treatment of ovarian cancer. Previous studies documented activity in patients with germline (gBRCA) and tumor (tBRCA) BRCA mutations (BRCAm) for treatment in lieu of chemotherapy as well as in recurrent ovarian cancer as maintenance therapy.The recent data from four randomized phase 3 trials have established an important role for frontline PARPi maintenance therapy in ovarian cancer. While SOLO-1 only included BRCAm patients, PRIMA, VELIA, and PAOLA-1 enrolled broader patient populations. The magnitude of benefit of PARPi in these studies was consistently greatest in the BRCAm patients (germline or tumor). PARPi treatment also improved PFS in the HRD cohort but to a lesser degree than in patients with BRCAm. In secondary analyses, the overall impact of PARPi treatment in HR proficient patients, which comprise about 50% of ovarian cancers, was more limited than in the other subgroups. Data for overall survival, also a secondary endpoint, is currently immature for these four trials. Fatigue, hematologic, and GI toxicities are the most commonly noted adverse events with PARPi therapy. The recent FDA approvals of PARPi in the maintenance setting will enable clinicians to incorporate these into frontline armamentarium of ovarian cancer treatment.

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