Abstract
BACKGROUND: Neoadjuvant administration of immune checkpoint inhibitors (ICIs) combined with chemotherapy demonstrated promising efficacy and manageable safety in locally advanced esophageal squamous cell carcinoma (ESCC). This prospective, single-arm, phase 2 study evaluated the efficacy and safety of neoadjuvant therapy with camrelizumab plus paclitaxel and nedaplatin for 2-4 cycles in ESCC. METHODS: Patients with locally advanced stage IIa-IIIb ESCC were enrolled in the study and received camrelizumab (200 mg), paclitaxel (155 mg/m 2 ), and nedaplatin (80 mg/m 2 ) intravenously on day one every 3 weeks. Patients underwent surgery after 2-4 cycles of treatment. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included the major pathological response (MPR) rate, R0 resection rate, tumor regression, objective response rate (ORR), and disease-free survival (DFS). Programmed cell death 1 ligand 1 (PD-L1) expression in tumor tissues was measured and quantified using immunohistochemistry staining and combined positive score (CPS), respectively. RESULTS: In total, 75 patients were enrolled and received neoadjuvant treatment. Of them, 45 (60%) received two cycles, 18 (24%) received three cycles, and 10 patients (13.3%) received four cycles of neoadjuvant therapy. Ultimately, 62 patients (82.7%) underwent surgery. The patients achieved a pCR of 27.4% (95% CI: 16.9-40.2), an MPR of 45.2% (95% CI: 33.1-59.2), and an ORR of 48.4% (95% CI: 35.5-61.4); all patients had an R0 resection. T and N downstaging occurred in 39 (62.9%) and 19 (30.6%) patients Moreover, patients with CPS ≥10 tended to have enhanced ORR, pCR, and MPR compared to those with CPS <10. Treatment-related adverse events (TRAEs) of grade 1-2 occurred in 59 (78.7%) patients, grade 3 TRAEs in four (5.3%), and one patient (1.3%) experienced a grade 4 TRAE. CONCLUSIONS: Neoadjuvant camrelizumab combined with chemotherapy showed promising efficacy in locally advanced ESCC, with a manageable safety profile, when administered flexibly in two to four cycles.