1. Olaparib plus bevacizumab first-line maintenance in ovarian cancer : final overall survival results from the PAOLA-1/ENGOT-ov25 trial
- Author
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I. Ray-Coquard, A. Leary, S. Pignata, C. Cropet, A. González-Martin, C. Marth, S. Nagao, I. Vergote, N. Colombo, J. Mäenpää, F. Selle, J. Sehouli, D. Lorusso, E.M. Guerra Alia, G. Bogner, H. Yoshida, C. Lefeuvre-Plesse, P. Buderath, A.M. Mosconi, A. Lortholary, A. Burges, J. Medioni, A. El-Balat, M. Rodrigues, T.-W. Park-Simon, C. Dubot, D. Denschlag, B. You, E. Pujade-Lauraine, P. Harter, Ray-Coquard, I, Leary, A, Pignata, S, Cropet, C, González-Martin, A, Marth, C, Nagao, S, Vergote, I, Colombo, N, Mäenpää, J, Selle, F, Sehouli, J, Lorusso, D, Alia, E, Bogner, G, Yoshida, H, Lefeuvre-Plesse, C, Buderath, P, Mosconi, A, Lortholary, A, Burges, A, Medioni, J, El-Balat, A, Rodrigues, M, Park-Simon, T, Dubot, C, Denschlag, D, You, B, Pujade-Lauraine, E, and Harter, P
- Subjects
Oncology ,advanced ovarian cancer ,overall survival ,Medizin ,Hematology ,bevacizumab ,olaparib - Abstract
Background: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. Patients and methods: Patients were randomized 2: 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. Results: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. Conclusions: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure. in press
- Published
- 2023