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

Lorusso D, Mouret-Reynier MA, Harter P, Cropet C, Caballero C, Wolfrum-Ristau P, Satoh T, Vergote I, Parma G, Nøttrup TJ, Lebreton C, Fasching PA, Pisano C, Manso L, Bourgeois H, Runnebaum I, Zamagni C, Hardy-Bessard AC, Schnelzer A, Fabbro M, Schmalfeldt B, Berton D, Belau A, Lotz JP, Gropp-Meier M, Gladieff L, Lück HJ, Abadie-Lacourtoisie S, Pujade-Lauraine E, Ray-Coquard I (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 34

Pages Range: 550-558

Journal Issue: 4

DOI: 10.1136/ijgc-2023-004995

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.

Involved external institutions

Arbeitsgemeinschaft Gynäkologische Onkologie e.V. (AGO) Germany (DE) Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) Italy (IT) Arcagy Gineco France (FR) Hospital General Universitari de València Spain (ES) Paracelsus Medizinische Privatuniversität Austria (AT) Fondazione Policlinico Universitario Agostino Gemelli IRCCS Italy (IT) Centre Jean-Perrin (UNICANCER) France (FR) Kliniken Essen-Mitte Germany (DE) Centre Léon-Bérard (UNICANCER) France (FR) University of Tsukuba / 筑波大学 Japan (JP) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Rigshospitalet Denmark (DK) Spanish Ovarian Cancer Research Group / Grupo Español de Cáncer de Ovario (GEICO) Spain (ES)

How to cite

APA:

Lorusso, D., Mouret-Reynier, M.A., Harter, P., Cropet, C., Caballero, C., Wolfrum-Ristau, P.,... Ray-Coquard, I. (2023). 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. International Journal of Gynecological Cancer, 34(4), 550-558. https://doi.org/10.1136/ijgc-2023-004995

MLA:

Lorusso, Domenica, et al. "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." International Journal of Gynecological Cancer 34.4 (2023): 550-558.

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