Primary Analysis of EPIK-O/ENGOT-ov61: Alpelisib Plus Olaparib Versus Chemotherapy in Platinum-Resistant or Platinum-Refractory High-Grade Serous Ovarian Cancer Without BRCA Mutation Journal Article
| Authors: | Konstantinopoulos, P. A.; Kim, J. W.; Freyer, G.; Lee, J. Y.; Gaba, L.; Grisham, R. N.; Colombo, N.; Wu, X. H.; Sehouli, J.; Cruz, F.; Cibula, D.; Monk, B. J.; Nyvang, G. B.; Friedlander, M.; Lorusso, D.; Van Nieuwenhuysen, E.; Malik, R.; Glasspool, R.; Marth, C.; Leary, A.; Cortés-Salgado, A.; Zamagni, C.; Marmé, F.; Sufliarsky, J.; Hinson, P.; Zuradelli, M.; Wang, C. G.; Su, F.; Paule, I.; Miller, M.; Matulonis, U. A.; González-Martín, A. |
| Article Title: | Primary Analysis of EPIK-O/ENGOT-ov61: Alpelisib Plus Olaparib Versus Chemotherapy in Platinum-Resistant or Platinum-Refractory High-Grade Serous Ovarian Cancer Without BRCA Mutation |
| Abstract: | <p>PURPOSEPatients with platinum-resistant/platinum-refractory high-grade serous ovarian cancer (HGSOC) without a BRCA mutation have poor prognosis and limited treatment options. We report efficacy and biomarker data from EPIK-O, which investigated alpelisib + olaparib versus single-agent chemotherapy in these patients.PATIENTS AND METHODSEPIK-O was an open-label, phase III trial that randomly assigned patients with platinum-resistant/platinum-refractory HGSOC with no germline or known somatic BRCA mutation 1:1 to alpelisib 200 mg once daily + olaparib 200 mg twice daily or treatment of physician's choice (TPC; paclitaxel 80 mg/m2 once weekly or pegylated liposomal doxorubicin 40-50 mg/m2 once every 28 days). Patients had 1-3 previous systemic therapies. Previous bevacizumab was required (unless contraindicated); previous poly(adenosine diphosphate-ribose) polymerase inhibitors were allowed. Primary end point was progression-free survival (PFS) per RECIST 1.1 (blinded independent review committee [BIRC]). Secondary efficacy end points included overall response rate (ORR; per BIRC), duration of response (per BIRC), and overall survival (OS; key secondary end point).RESULTSA total of 358 patients (alpelisib + olaparib [n = 180], TPC [n = 178]) were included. The median follow-up time was 9.3 months. At data cutoff (April 21, 2023), 33 (18.3%) and 30 (16.9%) patients remained on treatment with alpelisib + olaparib and TPC, respectively. The median PFS (BIRC) was 3.6 versus 3.9 months (hazard ratio [HR], 1.14 [95% CI, 0.88 to 1.48]; one-sided P = .84) for alpelisib + olaparib versus TPC. The ORR was 15.6% (95% CI, 10.6% to 21.7%) versus 13.5% (95% CI, 8.8% to 19.4%). The median OS was 10.0 versus 10.6 months (HR, 1.22; 95% CI, 0.87 to 1.71). The safety profile of alpelisib + olaparib was consistent with that observed for the individual agents.CONCLUSIONThe primary objective, PFS improvement, was not met in EPIK-O. No new or unexpected adverse events were observed. Biomarker analyses provided new insights for responders to alpelisib + olaparib.</p> |
| Keywords: | bevacizumab; germline; inhibitor; carcinoma; safety; therapy; expression; negative breast-cancer; open-label; mirvetuximab soravtansine |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 43 |
| Issue: | 26 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-09-10 |
| Language: | English |
| ACCESSION: | WOS:001563294600001 |
| DOI: | 10.1200/jco-25-00225 |
| PROVIDER: | wos |
| Notes: | Article -- Source: Wos |
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