Maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer: Main analysis of second progression-free survival in the phase III PAOLA-1/ENGOT-ov25 trial

• Published in: European journal of cancer (1990) 2022-10, Vol.174, p.221-231
• Main Authors: González-Martín, Antonio, Desauw, Christophe, Heitz, Florian, Cropet, Claire, Gargiulo, Piera, Berger, Regina, Ochi, Hiroyuki, Vergote, Ignace, Colombo, Nicoletta, Mirza, Mansoor R., Tazi, Youssef, Canzler, Ulrich, Zamagni, Claudio, Guerra-Alia, Eva M., Levaché, Charles B., Marmé, Frederik, Bazan, Fernando, de Gregorio, Nikolaus, Dohollou, Nadine, Fasching, Peter A., Scambia, Giovanni, Rubio-Pérez, María J., Milenkova, Tsveta, Costan, Cristina, Pautier, Patricia, Ray-Coquard, Isabelle
• Format: Article
• Language: English
• Subjects: Bevacizumab; Cancer; Chemotherapy; Death; Health hazards; Maintenance; Monoclonal antibodies; Mortality; Ovarian cancer; Placebos; Platinum; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Randomization; Ribose; Survival; Targeted cancer therapy
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.07.022

Background: PAOLA-1/ENGOT-ov25 (NCT02477644) demonstrated a significant progression-free survival (PFS) benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in newly diagnosed, advanced ovarian cancer. We report the prespecified main second progression-free survival (PFS2) analysis for PAOLA-1. Methods: This randomised, double-blind, phase III trial was conducted in 11 countries. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were in response after first-line platinum-based chemotherapy plus bevacizumab. Patients were randomised 2:1 to olaparib (300 mg twice daily) or placebo for up to 24 months; all patients received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months. Primary PFS end-point was reported previously. Time from randomisation to second disease progression or death was a key secondary end-point included in the hierarchical-testing procedure. Results: After a median follow-up of 35.5 months and 36.5 months, respectively, median PFS2 was 36.5 months (olaparib plus bevacizumab) and 32.6 months (placebo plus bevacizumab), hazard ratio 0.78; 95% confidence interval (CI) 0.64–0.95; P = 0.0125. Median time to second subsequent therapy or death was 38.2 months (olaparib plus bevacizumab) and 31.5 months (placebo plus bevacizumab), hazard ratio 0.78; 95% CI 0.64–0.95; P = 0.0115. Seventy-two (27%) patients in the placebo plus bevacizumab group received a poly(ADP-ribose) polymerase inhibitor as first subsequent therapy. No new safety signals were observed for olaparib plus bevacizumab. Conclusion: In newly diagnosed, advanced ovarian cancer, maintenance olaparib plus bevacizumab provided continued benefit beyond first progression, with a significant PFS2 improvement and a time to second subsequent therapy or death delay versus placebo plus bevacizumab.