Olaparib Plus Bevacizumab as First-Line Maintenance for Advanced Ovarian Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
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 bid; up to 24 months) plus bevacizumab (15 mg/kg q3w; 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 ITT (hazard ratio [HR]=0.92, 95% CI 0.76-1.12; P=0.4118). Subsequent poly(ADP-ribose) polymerase (PARP) 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 PARP inhibitors post-progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.
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Additional Info
Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial
ESMO Open 2023 May 19;[EPub Ahead of Print], 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, EMG Alia, G Bogner, H Yoshida, C Lefeuvre-Plesse, P Buderath, AM Mosconi, A Lortholary, A Burges, J Medioni, A El-Balat, M Rodrigues, TW Park-Simon, C Dubot, D Denschlag, B You, E Pujade-Lauraine, P HarterFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.