Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Aug 26;16(1):7950.
doi: 10.1038/s41467-025-62678-x.

Maintenance olaparib after platinum-based chemotherapy for advanced/metastatic endometrial cancer: GINECO randomized phase IIb UTOLA trial

Florence Joly  1 , Alexandra Leary  2 , Isabelle Ray-Coquard  3 , Bernard Asselain  4 , Manuel Rodrigues  5 , Laurence Gladieff  6 , Guillaume Meynard  7 , Sophie Abadie-Lacourtoisie  8 , Coriolan Lebreton  9 , Leïla Bengrine Lefevre  10 , Pierre Fournel  11 , Rémy Largillier  12 , Frédéric Selle  13 , Jean-Sébastian Frenel  14 , Yolanda Fernandez Diez  15 , Cyril Foa  16 , Philippe Follana  17 , Jérôme Meunier  18 , Michel Fabbro  19 , Anne-Claire Hardy Bessard  20 , Isabelle Cojean-Zelek  21 , Emilie Kaczmarek  22 , Elise Bonnet  23 , Antoine Arnaud  24 , Sophie Roche  25 , Karen Leroy  26 , Pierre-Alexandre Just  27 , Raphaël Leman  28 , Corinne Jeanne  28 , Céline Callens  29   30 , Benoit You  31 , Jérôme Alexandre  32
Affiliations
Clinical Trial

Maintenance olaparib after platinum-based chemotherapy for advanced/metastatic endometrial cancer: GINECO randomized phase IIb UTOLA trial

Florence Joly et al. Nat Commun. .

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: F.J. declares consulting/advisory board/speaker fees from GSK, Clovis, AstraZeneca, Roche, Eisai, Seagen, Tesaro, MSD, Astellas, Janssen, Ipsen, Bayer, Novartis/3A, and Pfizer; and travel expenses from Eisai, MSD, Ipsen, and GSK. A.L. declares personal honoraria from Medscape, GLG, and Servier; honoraria (to institution) for consulting/advisory roles from AstraZeneca, GSK, Zentalis, Owkin, Immunogen, and Apmonia; research funding (to institution) from AstraZeneca, GSK, MSD, Incyte, Eisai, Adaptimmune, Ziwig, Ose Immuno, and Zentalis; and travel/accommodation/expenses from AstraZeneca, Servier, and Ose Immuno. I.R.-C. declares honoraria from AbbVie, Advaxis, Agenus, Amgen, AstraZeneca, BMS, Clovis Oncology, Daiichi Sankyo, Deciphera, Genmab, GSK, Immunocore, Immunogen, MacroGenics, Mersana, MSD Oncology, Novartis, OxOnc, Pfizer, PharmaMar, PMV Pharma, Roche, Seagen, Sutro Biopharma, and Tesaro; consulting/advisory roles for AbbVie, Agenus, AstraZeneca, Blueprint Medicines, BMS, Clovis Oncology, Daichi, Deciphera, Eisai, Genmab, GSK, Immunocore, Immunogen, MacroGenics, Mersana, MSD Oncology, Novartis, Novocure, OSE Immunotherapeutics, Pfizer, PharmaMar, Roche, Seagen, Sutro Biopharma, and Tesaro; research funding (to institution) from BMS, MSD Oncology, and Roche/Genentech; and travel/accommodations/expenses from Advaxis, AstraZeneca, BMS, Clovis Oncology, Clovis Oncology, GSK, PharmaMar, Roche, and Tesaro. M.R. declares honoraria from Immunocore; consulting/advisory roles for Merck, AstraZeneca, and GSK; and research funding (to institution) from Johnson & Johnson and Merck. L.G. declares honoraria from GSK, AstraZeneca, and MSD; and travel/accommodation/expenses from GSK and MSD. G.M. declares consulting/advisory roles for Pfizer, Novartis, Lilly, Daiichi, and Eisai; and travel/accommodation/expenses from Pfizer. C.L. declares honoraria from GSK, MSD, AstraZeneca, and Eisai; consulting/advisory roles for GSK, AstraZeneca, AbbVie, and Eisai; and travel/accommodation/expenses from MSD and GSK. P.Fou. declares consulting/advisory roles for AstraZeneca, BMS, and MSD; research funding (to institution) from BMS and AstraZeneca; and travel/accommodation/expenses from Takeda. F.S. declares honoraria from AstraZeneca, MSD, GSK-Tesaro, Eisai, and Seagen; consulting/advisory roles for AstraZeneca, GSK-Tesaro, MSD, and AbbVie; and speakers’ bureau for AstraZeneca, MSD, GSK-Tesaro, and Eisai. J.-S.F. declares research funding from Seagen. P.Fol. declares consulting/advisory roles for AstraZeneca, Novartis, Daiichi, GSK, Eisai, MSD, and Lilly; expert testimony for AstraZeneca, Novartis, Daiichi, GSK, MSD, and Lilly; and travel/accommodation/expenses from AstraZeneca, Novartis, Daiichi, GSK, Eisai, MSD, and Lilly. M.F. declares honoraria from AstraZeneca; consulting/advisory role (to institution) for Tesaro/GSK; and travel/accommodations/expenses from Roche. E.B. declares honoraria from Gilead; and travel/accommodation/expenses from Lilly. K.L. declares honoraria from AstraZeneca, GSK, MSD, Lilly, Amgen, and Janssen; research funding from Roche; and travel/accommodation/expenses from Amgen. P.-A.J. declares honoraria from GSK, Eisai, and AstraZeneca. R.Le. declares honoraria from MSD; consulting/advisory roles for AstraZeneca and MSD; and travel/accommodation/expenses from AstraZeneca and MSD. C.C. declares consulting/advisory roles for AstraZeneca and MSD. B.Y. declares consulting roles for MSD, AstraZeneca, GSK-Tesaro, Bayer, Roche/Genentech, ECS Progastrin, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad, Menarini, Gilead, Eisai, and Pharma&; research funding from Gilead, Merck Serono, Roche, and Pfizer; and travel/accommodation/expenses from Roche/Genentech, AstraZeneca, BMS, MSD Oncology, Bayer, Boehringer Ingelheim, and Pfizer. J.A. declares honoraria from AstraZeneca, MSD, Eisai, GSK, Seagen, and Pfizer; consulting/advisory roles for AstraZeneca, MSD, GSK, Eisai, Seagen, and Pfizer; research funding from MSD, GSK, and Janssen; and travel/accommodation/expenses from AstraZeneca. The remaining authors declare no competing interests. Medical writing support was provided by Jennifer Kelly, MA (Medi-Kelsey Ltd, Ashbourne, UK), funded by GINECO.

Figures

Fig. 1
Fig. 1. Patient flow.
aPatient required radiotherapy. bIncluding non-RECIST progression in 2 patients. RECIST, Response Evaluation Criteria in Solid Tumors.
Fig. 2
Fig. 2. Investigator-assessed PFS estimated using Kaplan–Meier methodology.
A Intention-to-treat population (two-sided log-rank test stratified on predefined stratification factors). B p53-abnormal subgroup. C LGEhigh subgroup. D Subgroup with complete response to prior chemotherapy. CI confidence interval, LGE large genomic events, PFS progression-free survival. Vertical bars, censoring.
Fig. 3
Fig. 3. Investigator-assessed PFS in subgroups.
A p53-normal subgroup. B Subgroup with complete or partial response to prior chemotherapy. C Subgroup with stable disease with prior chemotherapy. CI confidence interval, PFS progression-free survival.
Fig. 4
Fig. 4. Overview of PFS by subgroup.
CI confidence interval, dMMR mismatch repair deficient, ECOG PS Eastern Cooperative Oncology Group performance status, HR hazard ratio, ITT intention-to-treat, LGE large genomic events, PFS progression-free survival, pMMR mismatch repair proficient.
Fig. 5
Fig. 5. Secondary efficacy endpoints in the intention-to-treat population.
A Time to first subsequent therapy (TFST). B Time to second disease progression or death (PFS2). C Time to second subsequent therapy (TSST). D Overall survival (OS). CI confidence interval.
Fig. 6
Fig. 6. Patient-reported outcomes.
A Evolution of EQ-5D-5L score over time. B Physical fatigue (per FA-12) over time. C QLQ-C30 GHS/HRQoL over time. D Time to first 10-point deterioration in GHS/HRQoL. CI confidence interval, GHS global health status, HRQoL health-related quality of life.
See this image and copyright information in PMC

References

    1. Coleman, R. L., Garside, J., Hurteau, J., Nguyen, J. & Kobayashi, M. Treatment patterns and outcomes among patients with advanced or recurrent endometrial cancer initiating first-line therapy in the United States. J. Health Econ. Outcomes Res.10, 82–90 (2023). - PMC - PubMed
    1. Jamieson, A. & McAlpine, J. N. Molecular profiling of endometrial cancer from TCGA to clinical practice. J. Natl. Compr. Cancer Netw.21, 210–216 (2023). - PubMed
    1. Levine, D. A. et al. Integrated genomic characterization of endometrial carcinoma. Nature497, 67–73 (2013). - PMC - PubMed
    1. Jamieson, A. et al. Clinical behavior and molecular landscape of stage I p53-abnormal low-grade endometrioid endometrial carcinomas. Clin. Cancer Res.29, 4949–4957 (2023). - PMC - PubMed
    1. Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature434, 917–921 (2005). - PubMed

Publication types

MeSH terms

Grants and funding

LinkOut - more resources