open access publication

Article, 2023

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial

ANNALS OF ONCOLOGY, ISSN 0923-7534, 0923-7534, Volume 34, 8, Pages 681-692, 10.1016/j.annonc.2023.05.005

Contributors

Ray-Coquard 0000-0003-2472-8306 (Corresponding author) [1] [2] [3] Leary, A. [1] [2] [4] Pignata, S. [5] [6] Cropet, C. [1] [2] [3] Gonzalez-Martin, A. [7] [8] Marth, C. [9] [10] Nagao, S. [11] [12] Vergote, I. [13] [14] [15] Colombo, N. [16] [17] [18] Maenpaa, J. [19] [20] [21] Selle, F. [1] [22] Sehouli, J. [23] [24] [25] [26] Lorusso, Domenica [6] [27] [28] Alia, Eva M. Guerra [8] [29] Bogner, G. 0000-0002-4495-1209 [10] [30] Yoshida, H. [31] Lefeuvre-Plesse, C. [1] [2] [32] [33] Buderath, P. [26] [34] Mosconi, A. M. [6] [35] Lortholary, A. [1] [36] Burges, A. [26] [37] Medioni, Jacques [1] [38] [39] [40] El-Balat, A. [26] [41] [42] [43] Rodrigues, M. [1] [2] [44] [45] [46] Park-Simon, T. W. 0000-0002-2863-3040 [26] [47] Dubot, C. [1] [2] [45] [46] [48] Denschlag, D. [26] [49] You, B. [1] [50] Pujade-Lauraine, E. [51] Harter, P. [26] [52] PAOLA-1 ENGOT-ov25 Invest

Affiliations

  1. [1] GINECO, Lyon, France
    2. [NORA names: France; Europe, EU; OECD];
  2. [2] Ctr Eugene Marquis, Dept Med Oncol, Rennes, France
    3. [NORA names: France; Europe, EU; OECD];
  3. [3] Ctr Leon BERARD, Dept Biostat, Lyon, France
    4. [NORA names: France; Europe, EU; OECD];
  4. [4] Inst Gustave Roussy, Dept Med, Gynecol Canc Unit, Villejuif, France
    5. [NORA names: France; Europe, EU; OECD];
  5. [5] IRCCS, Ist Nazl Tumori Fdn G Pascale, Dept Urol & Gynecol, Naples, Italy
    6. [NORA names: Italy; Europe, EU; OECD];

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 w60% 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 1/4 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.

Keywords

advanced ovarian cancer, bevacizumab, olaparib, overall survival

Data Provider: Clarivate

LINKS
-

Matching Records in NORA

  • No Matches Found

SUBJECTS
+

METRICS
+