e16139 Background: The prognosis for patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains poor. While immune checkpoint inhibitors have shown efficacy in advanced disease, their synergistic potential with concurrent chemoradiotherapy (CRT) in the neoadjuvant setting for LA-ESCC requires prospective validation. This study aimed to prospectively evaluate the efficacy and safety of the PD-L1 inhibitor adebrelimab combined with concurrent CRT as a novel neoadjuvant strategy for resectable LA-ESCC. Methods: This was a prospective, single-arm trial. Eligible patients had resectable thoracic ESCC, clinically staged as cT2N+ or cT3-4a any N M0. The regimen comprised adebrelimab (1200 mg intravenously every 3 weeks for 2 cycles) plus concurrent CRT (weekly paclitaxel/carboplatin and radiotherapy totaling 41.4 Gy in 23 fractions). Radical esophagectomy was scheduled 4-8 weeks after neoadjuvant therapy completion. The primary endpoint was the pathological complete response (pCR; ypT0N0) rate. Key secondary endpoints included the major pathological response (MPR; ≤10% residual viable tumor) rate, R0 resection rate, and safety. Results: Between June 2024 and October 2025, 32 patients were enrolled (median age 64.6 years; 75.0% male; 75.0% stage III). Of these, 24 patients proceeded to surgery, achieving a 100% (24/24) R0 resection rate. The primary endpoint was met, with a pCR rate of 58.3% (14/24). The MPR rate was 91.7% (22/24). Pathological downstaging was profound: 87.5% (21/24) of patients achieved primary tumor (T-stage) downstaging (ypT < cT), and 66.7% (16/24) achieved nodal clearance (ypN0). Regarding safety, grade ≥3 leukopenia occurred in 43.8% (14/32) of patients, all of whom had concomitant grade ≥3 lymphopenia. Common non-hematological toxicities included nausea (58.1%), constipation (54.8%), decreased appetite (48.4%), and vomiting (41.9%), which were all grade 1-2 and manageable with supportive care. Conclusions: Neoadjuvant adebrelimab plus concurrent CRT demonstrated remarkable efficacy in LA-ESCC, yielding high rates of pCR (58.3%) and MPR (91.7%), alongside significant pathological downstaging. While hematologic toxicity requires vigilant management, the profound tumor regression achieved offers a promising new strategy for improving outcomes in this population. These compelling results warrant further validation in a phase III randomized controlled trial. Future studies should explore optimization of the chemotherapy component to potentially enhance tolerability. Clinical trial information: ChiCTR2400084445.
Liang et al. (2026) studied this question.