A second chance? Outcomes of immunotherapy retreatment after prior checkpoint inhibitor exposure in endometrial and cervical cancer

OBJECTIVE(S): As immunotherapy (IO) is increasingly utilized for treatment of endometrial cancer (EC) and cervical cancer (CC), optimal treatment strategies after IO remains poorly defined. We evaluated clinical outcomes, treatment patterns, toxicity, and survival among patients with recurrent EC and CC who received IO after prior IO. METHODS: An Institutional Review Board approved, single-institution retrospective cohort study was conducted among patients with recurrent EC or CC treated with subsequent IO between January 1, 2017, and January 1, 2025. Patients were included if they received at least one dose of IO after prior IO. Clinical characteristics, immune-related adverse events, response, progression-free survival (PFS), and overall survival (OS) were abstracted from the electronic medical record. RESULTS: Of fifty eligible patients, 36 had EC and 14 had CC. Pembrolizumab was the most common first IO agent in both cohorts. Second IO regimens differed by disease site, with pembrolizumab plus lenvatinib most common in EC and pembrolizumab alone most common in CC. Following second IO exposure, objective response rate was 27.8% for EC and 14.3% for CC, while disease control rate was 55.6% and 64.3%, respectively. Median PFS with second IO exposure was 8.1 months in EC and 9.7 months in CC. Grade 3/4 immune-related adverse events occurred in 20.0% during second IO. CONCLUSIONS: IO retreatment demonstrated clinical activity in selected patients with recurrent EC and CC after prior IO, with disease control achieved in more than half of patients. Prospective studies are needed to define optimal patient selection and post-IO treatments.