Maintenance olaparib after platinum-based chemotherapy for advanced/metastatic endometrial cancer: GINECO randomized phase IIb UTOLA trial
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: Single-agent maintenance poly(ADP-ribose) polymerase (PARP) inhibition may represent an effective strategy in patients with advanced/metastatic endometrial cancer responding to platinum-based chemotherapy, including for molecular subtypes with suboptimal options. To explore this approach, we initiated the randomized phase IIb UTOLA trial (NCT03745950). Female patients without progression following front-line platinum-based chemotherapy for advanced/metastatic endometrial cancer were randomized 2:1 to twice-daily maintenance oral olaparib 300 mg or placebo until progression or intolerance, stratified by p53 status, mismatch repair status, and response to initial chemotherapy. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Secondary endpoints were PFS in subgroups, time to second progression or death, time to first and second subsequent therapy, objective response rate, overall survival, patient-reported outcomes, and safety. In the intention-to-treat population (n = 145), there was no PFS difference between olaparib and placebo (median 5.6 vs. 4.0 months, respectively; hazard ratio 0.94, 95% confidence interval 0.65–1.35; p = 0.74). However, intriguing numerical PFS effects were observed in exploratory analyses of pre-specified subgroups (p53-abnormal, complete response to initial chemotherapy, chromosomal instability). There was no overall survival difference between treatments. Grade 3/4 adverse events occurred in 36% versus 10% of olaparib- versus placebo-treated patients and were consistent with the olaparib safety profile in other cancers. Maintenance olaparib did not improve PFS, but promising numerical effects in subsets of patients warrant prospective evaluation. Single-agent maintenance PARP inhibition may represent an effective strategy for advanced/metastatic endometrial cancer treatment. Here this randomized phase IIb UTOLA trial evaluates the efficacy and safety of orally administered olaparib in female patients (n = 145) without progression following front-line platinum-based chemotherapy for advanced/metastatic endometrial cancer.
Source: Nature Communications
Authors: Florence Joly, Alexandra Leary, Isabelle Ray-Coquard, Bernard Asselain, Manuel Rodrigues, Laurence Gladieff, Guillaume Meynard, Sophie Abadie-Lacourtoisie, Coriolan Lebreton, Leïla Bengrine Lefevre, Pierre Fournel, Rémy Largillier, Frédéric Selle, Jean-Sébastian Frenel, Yolanda Fernandez Diez, Cyril Foa, Philippe Follana, Jérôme Meunier, Michel Fabbro, Anne-Claire Hardy Bessard, Isabelle Cojean-Zelek, Emilie Kaczmarek, Elise Bonnet, Antoine Arnaud, Sophie Roche, Karen Leroy, Pierre-Alexandre Just, Raphaël Leman, Corinne Jeanne, Céline Callens, Benoit You, Jérôme Alexandre
Institutions: Centre François Baclesse, Université de Caen Normandie, Institut Gustave Roussy, Fondation Gustave Roussy, Centre Léon Bérard, Arcagy Gineco, Institut Curie, Institut universitaire du cancer de Toulouse Oncopole, Centre Hospitalier Universitaire de Besançon, Institut de Cancérologie de l'Ouest, Institut Bergonié, Centre Georges François Leclerc, Centre Hospitalier Universitaire de Saint-Étienne, Centre Azuréen de Cancérologie, Groupe Hospitalier Diaconesses Croix Saint-Simon, Hôpital des Diaconesses, Institut de Cancérologie de Lorraine, Hôpital Saint Joseph, Centre Antoine Lacassagne, Centre hospitalier universitaire d'Orléans, Institut Regional du Cancer de Montpellier, Hôpital Intercommunal de Créteil, Centre Oscar Lambret, Groupe Hospitalier Mutualiste de Grenoble, Centre Jean Bernard, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Hôpital Cochin, Inserm, Université Paris Sciences et Lettres, Lyon 1 Université, Hospices Civils de Lyon, Centre pour l'innovation en cancérologie de Lyon
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4413645111