Scientific publications

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

May 19, 2023 | Magazine: Annals of Oncology

I Ray-Coquard  1 , A Leary  2 , S Pignata  3 , C Cropet  4 , A González-Martin  5 , C Marth  6 , S Nagao  7 , I Vergote  8 , N Colombo  9 , J Mäenpää  10 , F Selle  11 , J Sehouli  12 , D Lorusso  13 , E M Guerra Alia  14 , G Bogner  15 , H Yoshida  16 , C Lefeuvre-Plesse  17 , P Buderath  18 , A M Mosconi  19 , A Lortholary  20 , A Burges  21 , J Medioni  22 , A El-Balat  23 , M Rodrigues  24 , T-W Park-Simon  25 , C Dubot  26 , D Denschlag  27 , B You  28 , E Pujade-Lauraine  29 , P Harter  30 ; PAOLA-1/ENGOT-ov25 investigators

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 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.

CITATION  Ann Oncol. 2023 May 19;S0923-7534(23)00686-5. doi: 10.1016/j.annonc.2023.05.005