To evaluate the feasibility and efficacy of immune checkpoint inhibitor (ICI) rechallenge as second-line therapy in advanced esophageal squamous cell carcinoma (ESCC) patients who had progressed after first-line ICI-based treatment. This retrospective multicenter study analyzed 171 advanced ESCC patients who progressed after first-line ICI-based therapy and were subsequently re-treated with ICIs between 2021 and 2024. Rechallenge was defined as re-administration of the same or a different ICI agent. Patients were stratified by first-line treatment duration (≥180 vs. <180 days). Primary outcomes included progression-free survival during second-line treatment (PFS2) and overall survival (OS). Secondary outcomes included objective response rate (ORR), disease control rate (DCR), durable clinical benefit (DCB), and immune-related adverse events (irAEs). Patients who had a first-line treatment duration of ≥180 days had significantly longer PFS2 (5.70 vs. 3.47 months, P<0.001) and OS (14.77 vs. 12.92 months, P = 0.008). Among second-line strategies, immunotherapy alone provided the longest PFS2, while ICI plus chemotherapy resulted in the shortest (P<0.001). PD-L1 expression ≥1% was paradoxically associated with shorter PFS2. IrAEs during second-line treatment were not associated with improved efficacy. ICI rechallenge is a feasible and effective option for selected ESCC patients, particularly those with ≥180 days of benefit from first-line ICI therapy. Immunotherapy alone or combined with antiangiogenic agents may be preferable over combination with chemotherapy. Further prospective studies are needed to identify predictive factors and optimize rechallenge strategies.
Li et al. (Wed,) studied this question.