Phase III PAOLA-1/ENGOT-ov25 trial: Olaparib plus bevacizumab (bev) as maintenance therapy in patients (pts) with newly diagnosed, advanced ovarian cancer (OC) treated with platinum-based chemotherapy (PCh) plus bev

Abstract

Background: PAOLA‐1/ENGOT‐ov25 (NCT02477644) is the first phase III trial to evaluate the efficacy and safety of a PARP inhibitor with bev as first‐line (1L) maintenance therapy for advanced OC, regardless of BRCA1/2 mutation (BRCAm) status. Methods: PAOLA‐1 is a randomized, double‐blind, international phase III trial. Eligible pts had newly diagnosed, FIGO stage III‐IV, high‐grade serous or endometrioid OC, fallopian tube or primary peritoneal cancer. Pts had received standard PCh plus bev and were in clinical complete or partial response. Pts were randomized (2:1) to olaparib tablets (300 mg bid for up to 24 months [m]) plus bev (15 mg/kg, d1,q3w, for 15 m including when combined with PCh) or placebo (pbo) plus bev, stratified by 1L treatment outcome and tumour BRCAm status. The primary endpoint was investigator‐assessed progression‐free survival in the intent‐to‐ treat population (PFS; modified RECISTv1.1). Results: 537 pts were randomized to olaparib plus bev and 269 to pbo plus bev. Pt characteristics were well balanced. Median follow‐up was 22.7 m in the olaparib arm and 24.0 m in the pbo arm. PFS was significantly increased in the olaparib arm. PFS2 is immature. Grade >3 AEs were reported by 57% vs 51% of olaparib and pbo pts; the most common were hypertension (19% vs30%) and anaemia (17% vs< 1%). There were five treatment emergent AEs of death (olaparib, n= 1; pbo,n = 4). Olaparib and pbo dose interruptions, reductions and discontinuations occurred in 54% vs 24%, 41% vs 7% and 20% vs 6% of pts, respectively. There was no clinically meaningful difference in health‐related quality of life. Conclusions: Addition of olaparib to bev maintenance therapy following 1L PCh plus bev led to a statistically significant and clinically meaningful PFS benefit in pts with advanced OC. The PFS benefit in pts with a tBRCAm and in HRD‐positive pts was substantial.