P1.060. Long-Term Outcome of Adjuvant Chemoradiotherapy (CRT) Plus Pembrolizumab in Resectable Esophageal Squamous Cell Carcinoma (ESCC) at High Risk of Recurrence

Abstract

Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Adjuvant chemoradiotherapy followed by pembrolizumab (NCT03322267) has been shown to reduce relapses in patients at high risk of recurrence, including those with involved or close margins (≤1 mm), compared with a historical control cohort. This study evaluated long-term outcomes of this regimen. Methods Patients with resectable ESCC harboring high-risk recurrence features in tumor tissues after neoadjuvant chemoradiotherapy and esophagectomy—including involved or close margins (≤1 mm), extranodal extension of involved lymph nodes, or ypN2–3 disease—were enrolled in a single-arm phase II trial evaluating adjuvant cisplatin-based chemoradiotherapy (30 mg/m2 intravenously weekly for two cycles; 180–200 cGy per fraction for 10–13 fractions) followed by pembrolizumab (200 mg intravenously every 3 weeks for 18 cycles). A contemporary cohort with similar high-risk features was identified from a randomized phase II trial (NCT03623737). Progression-free survival (PFS), defined as the time from radical esophagectomy to disease recurrence or death, and overall survival (OS), defined as the time from radical esophagectomy to death, were compared between groups after long-term follow-up, with data locked on 1 December 2025. Survival outcomes were analyzed using the log-rank test, and baseline characteristics were summarized using descriptive statistics. Results From March 2017 to May 2024, 25 patients in the pembrolizumab cohort and 18 in the contemporary cohort were enrolled, with comparable median follow-up durations (59.4 vs 78.4 months). Baseline characteristics were generally balanced between groups, except for a higher proportion of lower post-neoadjuvant therapy stage and fewer patients receiving adjuvant CRT in the control group (P = 0.069 and 0.001, respectively). A trend toward improved median PFS was observed in the pembrolizumab cohort compared with controls (15.5 vs 5.3 months; P = 0.064; hazard ratio [HR], 0.53; 95% CI, 0.25–1.13), as well as improved median OS (22.9 vs 12.3 months; P = 0.066; HR, 0.52; 95% CI, 0.24–1.13). Subgroup analyses further demonstrated trends toward improved survival among patients with involved or close resection margins (≤1 mm), those who received adjuvant CRT, and those who were not enrolled in the randomized phase II trial. Conclusion Although there is potential selection bias from control cohort, adjuvant cisplatin-based chemoradiotherapy followed by one year of pembrolizumab demonstrated trends toward improved survivals in patients with residual pathologic disease and high-risk features after trimodality therapy for locally advanced ESCC (funded by Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc, Kenilworth, NJ (T.K.) [MISP# 55717] and NCTRC201703).