Objectives High-grade serous ovarian cancer (HGSOC) represents most epithelial ovarian cancers. Whilst initially responding to platinum-based therapy, ~75% of patients develop resistance, conferring poor prognosis. Homologous recombination repair proficiency is associated with platinum resistance and limited response to PARP inhibitors. PI3K pathway inhibition downregulates BRCA expression, abrogating homologous recombination repair proficiency, and may lead to (re)sensitization to PARP inhibitors. As alpelisib (PI3Kα inhibitor) + olaparib (PARP inhibitor) demonstrated preliminary synergism in platinum-resistant/refractory, BRCA-wild-type, recurrent HGSOC in a phase 1b study, the EPIK-O study is further evaluating this combination.
Methods EPIK-O/ENGOT-OV61 (NCT04729387) is a phase 3, randomized (1:1), open-label, active-controlled trial evaluating the efficacy and safety of alpelisib + olaparib versus single-agent chemotherapy in patients (N≈358) with no germline BRCA mutation, platinum-resistant/refractory HGSOC. Adult women with platinum-resistant/refractory, histologically confirmed HGSOC, high-grade endometrioid ovarian, fallopian tube, or primary peritoneal cancer, with no germline BRCA1/2 mutation, are included; patients must have received 1–3 prior systemic therapies. In Arm 1, patients receive alpelisib 200 mg orally OD + olaparib 200 mg orally BID; in Arm 2, patients receive paclitaxel 80 mg/m2 IV weekly or pegylated liposomal doxorubicin 40–50 mg/m2 IV Q28D (investigator’s choice). The primary endpoint is progression-free survival per radiologic tumor assessment (RECIST 1.1) by a blinded independent review committee. Key secondary endpoint is overall survival. Other secondary endpoints include overall response rate, clinical benefit rate, safety, and quality of life.
Results Enrollment is planned in 28 countries; completion of data collection for the primary endpoint is anticipated in 2023.
Conclusions Not applicable.
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