Journal Article Ahead of print 1 citation
PubMed: 42538280 DOI: 10.1016/j.ijgc.2026.104867
Efficacy and safety of immune checkpoint inhibitor rechallenge in cervical and endometrial cancer: a multi-center retrospective study (RICE study).
Int J Gynecol Cancer
Authors: Rayan Kabirian, Mathilde de Saint Ghislain, Olivia Le Saux, Laurent Mathiot, Jean-Sébastien Frenel, Paule Augereau, Alexandra Forestier, Jean David Fumet, Lauriane Eberst, Stanislas Quesada, Elsa Kalbacher, Céline Lescure, Thibault De La Motte Rouge, Juan Francisco Grau Bejar, Solenn Barraud, Thomas Genevee, Diana Bello Roufai, Manuel Rodrigues, Alexandra Leary
Affiliations
- Institut Curie, Department of Medical Oncology, Paris and Saint-Cloud, France.
- Oscar Lambret Center, Department of Gynecologic Oncology, Lille, France.
- Center Léon Bérard, Department of Medical Oncology, Lyon, France.
- Institut de Cancérologie de l'Ouest, Department of Medical Oncology, Site René Gauducheau, Saint Herblain, France.
- Oscar Lambret Center, Oncology Department, Internal Medicine, Lille, France.
- Université Bourgogne Europe, Centre Georges-François Leclerc, Unicancer, Cancer Biology Transfer Platform, UMR INSERM 1231, TIRECs Team, Dijon, France.
- Hôpitaux Universitaires de Strasbourg, Department of Medical Oncology, Strasbourg, France.
- Montpellier Cancer Institute (Institut du Cancer de Montpellier) (ICM), Department of Medical Oncology, Montpellier, France.
- Centre Hospitalier Universitaire de Besançon, Department of Medical Oncology, Besançon, France.
- Centre Eugène Marquis, Department of Medical Oncology, Rennes, France.
- INSERM U981, Université Paris-Saclay, Villejuif, France.
- Gustave Roussy, Department of Medical Oncology, Villejuif, France.
- Institut Curie, Department of Pharmacy, Paris and Saint-Cloud, France.
- Institut Curie, Department of Medical Oncology, Paris and Saint-Cloud, France.
- Institut Curie, Department of Medical Oncology, Paris and Saint-Cloud, France; Institut Curie, U1339/UMR3666, DNA Repair and Uveal Melanoma Unit, Paris, France.
- INSERM U981, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Department of Medical Oncology, Villejuif, France.
Abstract
OBJECTIVE
Immune checkpoint inhibitors have significantly improved the outcome of patients with cervical and endometrial cancers but the benefit of immune checkpoint inhibitor rechallenge is unknown. We aimed to evaluate the efficacy and safety of immune checkpoint inhibitor rechallenge in this population.
METHODS
This national retrospective study was conducted in 10 French academic centers between November 2015 and June 2025, to identify patients with metastatic cervical or endometrial cancer who were rechallenged with an immune checkpoint inhibitor. Rechallenge regimens included anti-programmed cell death protein 1/anti-programmed death-ligand 1 agents, administered alone or in combination with chemotherapy or targeted therapy. The primary endpoint was overall objective response rate during initial immune checkpoint inhibitor therapy and subsequent rechallenge. Secondary endpoints included progression-free survival following the initial and subsequent immune checkpoint inhibitor exposures, and safety (immune-related adverse events).
RESULTS
Thirty-nine patients with cervical (n = 20) or endometrial (n = 19) cancer who received immune checkpoint inhibitor rechallenge after prior immune checkpoint inhibitor exposure were identified. Ten patients who were rechallenged after prior immune checkpoint inhibitor exposure discontinuation for toxicity without subsequent disease progression were excluded from the efficacy analysis and retained for safety analysis only, yielding an efficacy cohort of 29 patients. Objective response rate was 76% (22/29) with prior immune checkpoint inhibitor exposure and 52% (15/29) upon rechallenge. Most patients received anti-programmed cell death protein 1-based therapy at rechallenge (92%), and 72% were treated without concurrent chemotherapy. Median progression-free survival decreased from 11.0 months (95% confidence interval 8.7 to 19.0) with prior immune checkpoint inhibitor exposure to 6.0 months (95% confidence interval 4.0 to 16.0) with immune checkpoint inhibitor rechallenge. Regarding safety, immune-related adverse events leading to prior immune checkpoint inhibitor exposure discontinuation were mainly colitis (32%) and hepatotoxicity (11%). During rechallenge, 13% of patients discontinued immune checkpoint inhibitor rechallenge due to toxicity.
CONCLUSIONS
Immune checkpoint inhibitor rechallenge in cervical and endometrial cancer is feasible, demonstrates meaningful anti-tumor activity, and is associated with a manageable safety profile.
MeSH
Cells, Confidence Intervals, Safety, Progression-Free Survival, Retrospective Studies, Neoplasms, Multiple Chronic Conditions, Drug Therapy, Drug-Related Side Effects And Adverse Reactions, Immune Checkpoint Inhibitors, Apoptosis Regulatory Proteins, Therapeutics, Programmed Cell Death 1 Receptor, Cell Death, Endometrial Neoplasms, Chemotherapy