Abstract
BACKGROUND: Nivolumab is effective in treating patients with esophageal squamous cell carcinoma (ESCC). The efficacy of nivolumab in combination with neoadjuvant chemoradiotherapy (CRT) remains unclear. METHODS: In this phase II trial with Simon's 2-stage design, neoadjuvant nivolumab, paclitaxel, and cisplatin were administered with radiotherapy followed by esophagectomy to patients with locally advanced ESCC. The primary endpoint was pathological complete response (pCR). The secondary endpoints were feasibility, safety, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 17 patients were enrolled in stage I. Fourteen patients received esophagectomy, with pCR achieved in 4, below the criterion for continuing to stage II. All grade and ≥grade 3 treatment emergent adverse events (TEAEs) occurred in 15 and 4 patients, respectively. Immune-related TEAEs occurred in 7; none were ≥ grade 3. The median durations of RFS, PFS, and OS were 8, 12, and 25 months, respectively. Patients with high expression of PD-L1 had higher pCR rate (100% vs 18%, P = 0.019). CONCLUSIONS: Nivolumab in combination with neoadjuvant CRT is safe for patients with locally advanced ESCC, and may be beneficial in those with high PD-L1 expression. CLINICAL TRIAL REGISTRATION: NCT05130684.