Update results of benmelstobart (BEN) combined with concurrent chemoradiotherapy (cCRT) versus cCRT alone as neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC): A multicentre, randomised study.

Abstract

e16112 Background: Standard neoadjuvant concurrent chemoradiotherapy (cCRT) for resectable ESCC yields only a 20-30% pathological complete response (pCR) rate. With immunotherapy has been approved for advanced ESCC, exploring its combination with cCRT in the neoadjuvant setting is imperative. Methods: This multicentre, randomised phase II trial planned to enroll 100 patients with resectable ESCC (T1-3N+M0/T3NanyM0). Patients were randomised 1:1 to benmelstobart (BEN) + cCRT or cCRT alone, stratified by cT stage (T1-2 vs T3). The BEN+cCRT group received BEN (1200mg, D1 and 22) plus cCRT (paclitaxel/carboplatin, 41.4 Gy/23 fraction of radiotherapy), while the cCRT group received cCRT alone. Surgery followed 6-8 weeks later. The primary endpoint was pCR rate in primary tumor site and lymph node. Secondary endpoints included MPR, ORR, DCR, R0 resection, 1-year DFS/OS rate, and safety. A preplanned radiation de-escalation to 36 Gy would be triggered if > 18 of the first 30 BEN+cCRT patients achieved pCR in first stage. Results: From Oct 24, 2024, to Nov 20, 2025, 82 patients were randomised to BEN+cCRT (n = 42) or cCRT alone (n = 40). Four patients in BEN+cCRT group withdrew after randomization without treatment. In the full analysis set (FAS), 38 and 40 patients were analyzed, respectively. 73.1% of patients were ECOG PS 1. 16.7% of patients had primary tumor in upper esophagus. Thirty-seven and 40 patients completed neoadjuvant therapy, respectively. The ORR was 55.3% vs 60.0% in each group. Surgery rates were 73.7% (28/38) vs 90.0% (36/40). Of them, the primary endpoint pCR rates were 50.0% (14/28) vs 36.1% (13/36); MPR rates were 89.3% (25/28) vs 61.1% (22/36), respectively. Grade ≥3 TEAEs occurred in 73.7% vs 60.0% of patients, with hematologic toxicity being the most common. No grade ≥3 radiation esophagitis or grade 5 TEAEs were observed. Conclusions: Despite not meeting the prespecified endpoint of the first stage and without a radiotherapy dose reduction, BEN plus cCRT shows potential efficacy as neoadjuvant therapy in resectable ESCC, with encouraging pCR rate, MPR rate and a manageable safety profile. Clinical trial information: NCT06637163 . The pathological and surgical outcomes. Patients had surgery Patients had surgery FAS FAS BEN+cCRT (n=28) cCRT (n=36) BEN+cCRT (n=38) cCRT (n=40) pCR rate, n (%) 14 (50.0%) 13 (36.1%) 14 (36.8%) 13 (32.5%) pCR rate in primary tumor site, n (%) 17 (60.7%) 16 (44.4%) 17 (44.7%) 16 (40.0%) MPR rate, n (%) 25 (89.3%) 22 (61.1%) 25 (65.8%) 22 (55.0%) R0 resection, n (%) 28 (100%) 35 (97.2%) 28 (73.7%) 35 (87.5%) Tumor regression grade, n (%) 0 / 1 17 (60.7%) / 8 (28.6%) 16 (44.4%) / 5 (13.9%) 17 (44.7%) / 8 (21.1%) 16 (40.0%) / 5 (12.5%) 2 / 3 1 (3.6%) / 1 (3.6%) 8 (22.2%) / 6 (16.7%) 1 (2.6%) / 1 (2.6%) 8 (20.0%) / 6 (15.0%) Missing 1 (3.6%) 1（2.8%） 11 (28.9%) 5（12.5%）