Updated progression-free survival and final overall survival with 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

Domenica Lorusso, Marie Ange Mouret-Reynier, Philipp Harter, Claire Cropet, Cristina Caballero, Pia Wolfrum-Ristau, Toyomi Satoh, Ignace Vergote, Gabriella Parma, Trine J. Nøttrup, Coriolan Lebreton, Peter A. Fasching, Carmela Pisano, Luis Manso, Hugues Bourgeois, Ingo Runnebaum, Claudio Zamagni, Anne Claire Hardy-Bessard, Andreas Schnelzer, Michel FabbroBarbara Schmalfeldt, Dominique Berton, Antje Belau, Jean Pierre Lotz, Martina Gropp-Meier, Laurence Gladieff, Hans Joachim Lück, Sophie Abadie-Lacourtoisie, Eric Pujade-Lauraine, Isabelle Ray-Coquard

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Objective In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status. Methods Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This post hoc analysis evaluated 5-year progression-free survival and mature overall survival in patients classified by clinical risk and HRD status. Results Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk. Conclusion This post hoc analysis indicates that in patients with newly diagnosed advanced HRD-positive ovarian cancer, maintenance olaparib plus bevacizumab should not be limited to those considered at higher risk of disease progression. Five-year progression-free survival rates support long-term remission and suggest an increased potential for cure with particular benefit suggested in lower-risk HRD-positive patients.

Original languageEnglish
Pages (from-to)550-558
Number of pages9
JournalInternational Journal of Gynecological Cancer
Volume34
Issue number4
DOIs
StatePublished - 21 Dec 2023
Externally publishedYes

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