Preoperative conversion therapy of camrelizumab combined with paclitaxel and nedaplatin for unresectable advanced esophageal squamous cell carcinoma: a phase 2 study.

Abstract

Patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) face limited treatment options and poor outcomes. Preclinical evidence supports chemoimmunotherapy as a conversion therapy; therefore, this study aims to evaluate the efficacy and safety of preoperative camrelizumab with paclitaxel and nedaplatin. Patients received a combination of camrelizumab (200 mg), paclitaxel (155 mg/m²), and nedaplatin (80 mg/m²) every 3 weeks. An efficacy assessment was performed every two cycles using the RECIST v1.1 criteria, and patients in the resected group underwent surgery 4-6 weeks after the last dose. The primary endpoint was 1-year overall survival (OS) rate, while secondary endpoints included surgical conversion rates, pathological response rates, objective response rate (ORR), disease-free survival (DFS), and safety. This trial enrolled 141 patients with unresectable ESCC (132 locally advanced [M0], 9 metastatic [M1]) with a median follow-up of 32.2 months. Post-induction ORR was 56.7%. The intention-to-treat (ITT) conversion rate reached 48.9% overall and 50.0% (66/132) in M0 patients (R0: 100%; pathological complete response (pCR): 20.9%; major pathological response: 55.2%). One-year OS was 78.7%. Surgical conversion significantly improved survival overall (median OS: not reached (NR) vs. 14.1 months; hazard ratio (HR) = 0.22; 95% CI, 0.13-0.37; P < 0.0001), with further benefit in objective responders (median OS: NR vs. 20.9 months; HR = 0.30; 95% CI, 0.14-0.61; P < 0.001). Approximately 75.9% of patients experienced treatment-related adverse events (TRAEs), predominantly mild to moderate. Pan-lactylation levels were significantly elevated in non-pCR ESCC compared to pCR tissues. A peritumoral radiomic features-derived model effectively stratified patients into distinct groups with significantly different OS and DFS. The chemoimmunotherapy regimen shows promising efficacy as a conversion therapy in improving surgical resectability and survival outcomes with manageable TRAEs, and does not delay surgery. ChiCTR2100046355.