Real-world efficacy of immune checkpoint inhibitor rechallenge in patients with advanced esophageal squamous cell carcinoma: A retrospective study.

Abstract

e16046 Background: Immunotherapy combined with chemotherapy is the standard first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC). However, data regarding the efficacy of sequential immune checkpoint inhibitor (ICI) therapy following disease progression are limited. This study evaluates the real-world clinical efficacy of immune rechallenge in advanced ESCC patients to identify optimal strategies for overcoming resistance. Methods: This single-center, retrospective study analyzed patients with advanced ESCC treated at the First Affiliated Hospital of Zhengzhou University between Jan 1, 2020, and Dec 31, 2024. Eligible patients received ≥2 cycles of ICI-based therapy in both 1L and 2L settings. Primary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Subgroup analyses were performed based on different 2L treatment regimens. Results: A total of 135 patients were enrolled (median age: 64 years; 71% male). The median PFS for second-line treatment (mPFS2) was 7.23 months (95% CI: 5.75–9.30). The ORR and DCR were 14.81% and 69.63%, respectively. Subgroup analysis by 2L regimen revealed that the triple combination (ICI + anti-angiogenic targeted therapy + chemotherapy, n = 39) achieved the longest mPFS2 of 9.03 months (95% CI: 5.95–25.00), followed by ICI + anti-angiogenic therapy (n = 39) with 6.77 months (95% CI: 4.96–11.66), ICI + chemotherapy (n = 48) with 5.75 months (95% CI: 4.07–9.66), and ICI monotherapy (n = 9) with 4.67 months (95% CI: 2.73–NR). Multivariate COX regression identified the triple combination as an independent prognostic factor for improved PFS2. Regarding target consistency, patients maintaining the same immune checkpoint target (n = 123, 91.11%) achieved an mPFS2 of 7.23 months (95% CI: 5.75–9.66), compared to 6.37 months (95% CI: 2.60–NR) in those who switched targets (n = 12). Notably, efficacy was independent of the duration of response to prior 1L treatment (PFS1 < 6 months vs. ≥6 months). Conclusions: Immune rechallenge represents a viable therapeutic strategy for advanced ESCC. The triple combination of immunotherapy, anti-angiogenic targeted therapy, and chemotherapy yielded the optimal progression-free survival benefit. Furthermore, maintaining the original immune checkpoint target demonstrated a trend toward superior efficacy compared to switching targets, and efficacy was observed regardless of the duration of benefit from prior first-line treatment. Clinical trial information: ChiCTR2500113885. Subgroup analysis of efficacy. n mPFS2（m） ORR（%） DCR（%） ITT 135 7.23 14.8 69.6 2L treatment I 9 4.67 0 66.7 I+C 48 5.75 12.5 56.3 I+A 39 6.77 20.5 87.2 I+C+A 39 9.03 15.4 69.2 Target Consistency Same Target (Yes) 123 7.23 15.5 68.3 Switch Target (No) 12 6.37 8.3 83.3