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Updated: Aug 5, 2026
In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
Efficacy and safety of immune checkpoint inhibitor rechallenge in cervical and endometrial cancer: a multi-center
Rayan Kabirian1, Mathilde de Saint Ghislain2, Olivia Le Saux3
1Institut Curie, Department of Medical Oncology, Paris and Saint-Cloud, France.
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.
