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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

Purpose - Patients 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 chemothera...

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Main Authors: Konstantinopoulos, Panagiotis A. (Author) , Kim, Jae Weon (Author) , Freyer, Gilles (Author) , Lee, Jung Yun (Author) , Gaba, Lydia (Author) , Grisham, Rachel N. (Author) , Colombo, Nicoletta (Author) , Wu, Xiaohua (Author) , Sehouli, Jalid (Author) , Cruz, Felipe (Author) , Cibula, David (Author) , Monk, Bradley J. (Author) , Nyvang, Gitte-Bettina (Author) , Friedlander, Michael (Author) , Lorusso, Domenica (Author) , Van Nieuwenhuysen, Els (Author) , Malik, Rozita (Author) , Glasspool, Rosalind (Author) , Marth, Christian (Author) , Leary, Alexandra (Author) , Cortés-Salgado, Alfonso (Author) , Zamagni, Claudio (Author) , Marmé, Frederik (Author) , Sufliarsky, Jozef (Author) , Hinson, Patsy (Author) , Zuradelli, Monica (Author) , Wang, Craig (Author) , Su, Fei (Author) , Paule, Ines (Author) , Miller, Michelle (Author) , Matulonis, Ursula A. (Author) , González-Martín, Antonio (Author)
Format: Article (Journal)
Language:English
Published: September 10, 2025
In: Journal of clinical oncology
Year: 2025, Volume: 43, Issue: 26, Pages: 2908-2917
ISSN:1527-7755
DOI:10.1200/JCO-25-00225
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1200/JCO-25-00225
Verlag, kostenfrei, Volltext: https://ascopubs.org/doi/10.1200/JCO-25-00225
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Author Notes:Panagiotis A. Konstantinopoulos, MD, PhD ; Jae Weon Kim, MD, PhD ; Gilles Freyer, MD, PhD ; Jung Yun Lee, MD, PhD ; Lydia Gaba, MD ; Rachel N. Grisham, MD ; Nicoletta Colombo, MD, PhD ; Xiaohua Wu, MD, PhD ; Jalid Sehouli, MD ; Felipe Cruz, MD, PhD ; David Cibula, MD, PhD ; Bradley J. Monk, MD ; Gitte-Bettina Nyvang, MD ; Michael Friedlander, MBChB, PhD ; Domenica Lorusso, MD, PhD ; Els Van Nieuwenhuysen, MD, PhD ; Rozita Malik, MBBS ; Rosalind Glasspool, MD, PhD ; Christian Marth, MD, PhD ; Alexandra Leary, MD, PhD ; Alfonso Cortés-Salgado, MD; Claudio Zamagni, MD; Frederik Marmé, MD, PhD; Jozef Sufliarsky, MD, PhD; Patsy Hinson; Monica Zuradelli, MD; Craig Wang, PhD; Fei Su, PhD ; Ines Paule, PhD; Michelle Miller, MD, MPH; Ursula A. Matulonis, MD ; and Antonio Gonz ´alez-Mart´ın, MD, PhD
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Summary:Purpose - Patients 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 Methods - EPIK-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). - Results - A 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. - Conclusion - The 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.
Item Description:Online veröffentlicht: 23. Juli, 2025
Gesehen am 13.11.2025
Physical Description:Online Resource
ISSN:1527-7755
DOI:10.1200/JCO-25-00225

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