Subject terms
tumor, fatigue, ESCC, esophageal squamous cell carcinomas, esophageal squamous cell carcinoma, anorexia
OESOPHAGEAL SQUAMOUS CELL CARCINOMA, TUMOR, INFILTRATION, ADVERSE EVENTS, SECONDARY, ANOREXIA
Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results of a phase 1b trial of neoadjuvant PD-L1 blockade with adebrelimab in resectable ESCC. Patients received two neoadjuvant doses of adebrelimab followed by surgery. The primary endpoints were safety and feasibility; secondary endpoints included pathologic complete response (pCR) and OS. Our data showed the primary endpoints of safety and feasibility had been met. Common treatment-related adverse events were anorexia (32%) and fatigue (16%), without grade 3 or more adverse events. Of the 30 patients enrolled in the trial, 25 underwent successful resection without surgery delay and 24% had major pathologic responses including a pCR rate of 8%. The 2-year OS was 92%. Responsive patients had an immune-enriched tumor microenvironment phenotype, whereas nonresponsive patients had greater infiltration of cancer-associated fibroblasts at baseline. Clonotypic dynamics of pre-existing intratumoral T cells was a hallmark of responsive patients. These findings provide a rational for neoadjuvant anti-PD-L1 monotherapy as a therapeutic strategy for patients with resectable ESCC. ClinicalTrials.gov identifier: In the NATION-1907 trial, treatment of patients with resectable esophageal squamous cell carcinoma with the anti-PD-L1 agent adebrelimab was safe and showed preliminary overall survival efficacy, with responders exhibiting an immune-enriched tumor microenvironment phenotype at baseline.