Perioperative adebrelimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma: A single-arm, open-label, multicenter study.

Abstract

421 Background: Neoadjuvant programmed cell death 1 (PD-1) inhibitors combined with chemotherapy have shown promising results in treating locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, relatively little attention has been focused on programmed cell death ligand 1 (PD-L1) blockades. This study aims to evaluate the efficacy and safety of neoadjuvant adebrelimab (anti-PD-L1 antibody) plus chemotherapy followed by adjuvant adebrelimab for resectable LA-ESCC. Methods: In this single-arm, multicenter study, patients (pts) with newly diagnosed, locally advanced resectable thoracic ESCC (cT1b-2, N+ or cT3-4a, N0/+) received 2 cycles of neoadjuvant chemoimmunotherapy with adebrelimab (1200 mg), paclitaxel (175 mg/m 2 ) and cisplatin (75 mg/m 2 ) every 3 weeks, followed by esophagectomy and 16 doses of adebrelimab. The primary endpoints were safety and pathological complete response (pCR) rate. Secondary endpoints included surgery completion rate, R0 resection rate, major pathological response (MPR) rate, event-free survival (EFS) and disease-free survival (DFS). The trial was registered at Chinese Clinical Trial Registry, identifier: ChiCTR2300069179. Results: Between May 2023 and January 2024, 36 pts met inclusion criteria, with a median age of 65 years (range: 42-73). Of these, 66.7% (24/36) were classified as stage III-IVa. As of August 1, 2024, the median number of treatment cycles for all pts was 7 (interquartile range, 2-12). The neoadjuvant therapy completion rate was 91.7% (33/36). Thirty-two pts underwent minimally invasive esophagectomy, resulting in an overall surgical resection rate of 88.9% and an R0 resection rate of 90.6%. The pCR rate was 15.6% (5/32) and the MPR rate was 31.2% (10/32). The EFS and DFS outcomes were not mature. During the preoperative treatment period, 35 pts (97.2%) experienced any grade of treatment-related adverse events (TRAEs). Grade 3 or 4 TRAEs occurred in 7 pts (19.4%), and there were no grade 5 TRAEs. The most common grade 3/4 adverse events included neutropenia (11.1%), leukopenia (5.6%), diarrhea (5.6%) and hyponatremia (5.6%). Surgical complications of grade 3/4 were reported in 7 pts (21.9%), with anastomotic fistula (6.3%) being the most common. No perioperative deaths occurred. Conclusions: Neoadjuvant adebrelimab combined with chemotherapy and adjuvant adebrelimab demonstrated encouraging clinical efficacy and manageable safety in pts with LA-ESCC. Further study is warranted. Clinical trial information: ChiCTR2300069179.