Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial

Philipp Harter,Claire Cropet,Barbara Schmalfeldt,Michel Fabbro,Trine Jakobi Nøttrup,Keiichi Fujiwara,Marie Ange Mouret-Reynier,Sandro Pignata,Antonio González-Martín,Gerhard Bogner,Anne Floquet,Nicoletta Colombo,Giovanni Scambia,Ignace Vergote,Éric Pujade-Lauraine ,Eva María Guerra Alía ,Anne‐Claire Hardy‐Bessard ,Ingo B Runnebaum ,Ahmed El‐Balat ,Isabelle Ray‐Coquard

doi:10.1016/j.ygyno.2021.12.016

Abstract

ObjectivesAdding maintenance olaparib to bevacizumab provided a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the randomized, double-blind PAOLA-1/ENGOT-ov25 trial (NCT02477644). We analyzed PFS by clinical risk and biomarker status. MethodsPatients received olaparib 300 mg twice daily for up to 24 months plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total, or placebo plus bevacizumab. This post hoc exploratory analysis evaluated PFS in patients classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by biomarker status. ResultsOf 806 randomized patients, 74% were higher risk and 26% were lower risk. After a median 22.9 months of follow-up, PFS favored olaparib plus bevacizumab versus placebo plus bevacizumab in higher-risk patients (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.49–0.74) and lower-risk patients (0.46; 0.30–0.72). Olaparib plus bevacizumab provided a substantial PFS benefit versus bevacizumab alone in the homologous recombination deficiency (HRD)-positive subgroup (higher risk: HR 0.39; 95% CI 0.28–0.54 and lower risk: 0.15; 0.07–0.30), with 24-month PFS rates in lower-risk patients of 90% versus 43%, respectively (Kaplan–Meier estimates). ConclusionsIn PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit in HRD-positive patients with a reduction of risk of progression or death of 61% in the higher-risk group and of 85% in the lower-risk group compared with bevacizumab alone.

Highlights

Patients with newly diagnosed, advanced ovarian cancer undergo cytoreductive surgery and platinum-based chemotherapy with curative intent
Olaparib plus bevacizumab provided a substantial progression-free survival (PFS) benefit versus bevacizumab alone in the homologous recombination deficiency (HRD)-positive subgroup, with 24-month PFS rates in lower-risk patients of 90% versus 43%, respectively (Kaplan–Meier estimates)
In PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit in HRDpositive patients with a reduction of risk of progression or death of 61% in the higher-risk group and of 85% in the lower-risk group compared with bevacizumab alone

Summary

Introduction

Patients with newly diagnosed, advanced ovarian cancer undergo cytoreductive surgery and platinum-based chemotherapy with curative intent. Maintenance therapy with the poly(ADP–ribose) polymerase (PARP) inhibitor olaparib alone provided a substantial PFS benefit compared with placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation (BRCAm) in the phase III SOLO1 trial (HR 0.30; 95% CI 0.23–0.41; P < 0.001) [7]. Based on these results, maintenance olaparib is approved in the USA, the EU, China, Japan and other countries worldwide for women with a BRCAm [8,9,10,11]

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