Maintenance olaparib after platinum-based chemotherapy for advanced/metastatic endometrial cancer: GINECO randomized phase IIb UTOLA trial
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.
Authors
- Laurence Gladieff (ORCID: https://orcid.org/0000-0002-6980-9719)
- Cyril Foa
- Coriolan Lebreton (ORCID: https://orcid.org/0000-0002-4275-1721)
- Alexandra Léary (ORCID: https://orcid.org/0000-0002-2043-2244)
- Sophie Roche (ORCID: https://orcid.org/0000-0001-6751-0636)
- Céline Callens (ORCID: https://orcid.org/0000-0003-3377-4937)
- Isabelle Cojean-Zelek
- P. Fournel (ORCID: https://orcid.org/0000-0002-3884-6816)
- Jean‐Sébastien Frenel (ORCID: https://orcid.org/0000-0002-5273-0561)
- Sophie Abadie‐Lacourtoisie
- Florence Joly (ORCID: https://orcid.org/0000-0001-6168-4942)
- Manuel Rodrigues (ORCID: https://orcid.org/0000-0002-5443-0802)
- Elise Bonnet (ORCID: https://orcid.org/0000-0002-7061-0993)
- Karen Leroy (ORCID: https://orcid.org/0000-0002-4379-0140)
- Yolanda Fernandez Diez
- Frédèric Selle (ORCID: https://orcid.org/0000-0002-7016-5383)
- Emilie Kaczmarek (ORCID: https://orcid.org/0000-0002-2633-3773)
- Isabelle Laure Ray-Coquard (ORCID: https://orcid.org/0000-0003-2472-8306)
- Benoît You (ORCID: https://orcid.org/0000-0002-3177-8857)
- Jérôme Meunier
- Raphaël Leman (ORCID: https://orcid.org/0000-0003-1978-7133)
- Guillaume Meynard (ORCID: https://orcid.org/0000-0002-0646-4055)
- Michel Fabbro (ORCID: https://orcid.org/0000-0003-1910-4777)
- Jérôme Alexandre (ORCID: https://orcid.org/0000-0001-5252-5800)
- Bernard Asselain
- Corinne Jeanne
- Antoine Arnaud
- Anne-Claire Hardy- Bessard
- Philippe Follana (ORCID: https://orcid.org/0000-0001-6999-462X)
- L. Bengrine Lefevre
- Rémy Largillier
- Pierre-Alexandre Just (ORCID: https://orcid.org/0000-0002-0458-4117)
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Inserm (FR)
- Université Paris Cité (FR)
- Institut Gustave Roussy (FR)
- Centre Hospitalier Universitaire de Besançon (FR)
- Hôpital Cochin (FR)
- Centre Georges François Leclerc (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Institut de Cancérologie de Lorraine (FR)
- Hospices Civils de Lyon (FR)
- Centre François Baclesse (LU)
- Hôpital Européen Georges-Pompidou (FR)
- Centre Léon Bérard (FR)
- Institut de Cancérologie de l'Ouest (FR)
- Hôpital Européen (FR)
- Groupe Hospitalier Mutualiste de Grenoble (FR)
- Groupe Hospitalier Diaconesses Croix Saint-Simon (FR)
- Institut Génétique Nantes Atlantique (FR)
- Hôpital Saint Joseph (FR)
- Centre François Baclesse (FR)
- Centre Jean Bernard (FR)
- Institut Claudius Regaud (FR)
- Centre Oscar Lambret (FR)
- Centre Azuréen de Cancérologie (FR)
- Institut Bergonié (FR)
- Arcagy Gineco (FR)
- Institut de Recherche en Cancérologie de Montpellier (FR)
- Centre hospitalier universitaire d'Orléans (FR)
- Centre Antoine Lacassagne (FR)
- Centre Hospitalier Universitaire de Saint-Étienne (FR)
- Hôpital Intercommunal de Créteil (FR)
- Institut Curie (FR)
- Meritor (France) (FR)
- HCL Technologies (India) (IN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-26
- DOI
- https://doi.org/10.1038/s41467-025-62678-x
- Citations
- 4
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 4.18
Funders
- Amgen
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Gilead Sciences
- Clovis Oncology
- Seagen
- Eisai
- Genentech