Neoadjuvant sintilimab and chemotherapy for resectable esophageal squamous cell carcinoma: a prospective, single-arm, phase II study

Abstract Background: Combining PD-1 blockade with chemotherapy has widely used in first line treatment of metastatic esophageal squamous cell carcinoma (ESCC). However, their efficacy as neoadjuvant therapy in resectable ESCC is little known. This study was performed to assess the activity and safety profile of the combination of sintilimab and chemotherapy in the neoadjuvant treatment of ESCC. Methods: In this single-arm, phase II study, we recruited patients with histopathologically diagnosed resectable ESCC who had clinical cT1-3/N0-1M0 (stage II-Ⅲ). Patients were given sintilimab (200mg, iv, d1) in combined with chemotherapy (nab-paclitaxel 260 mg/m2, d1 and cisplatin 75 mg/m2, d1-3) every 3 weeks for 2 cycles. The primary endpoint was pathological complete response (pCR). Results：Between Nov 2020 and Nov 2022, 29 patients were enrolled and 27 patients completed the two cycles of neoadjuvant therapy. A total of 21 patients underwent surgery without treatment-related surgical delay. The major pathologic response (MPR) rate was 42.9% (9/21) and the pathologic complete response (pCR) rate was 28.6% (6/21). The most frequent grade 3 or 4 treatment-related adverse events (TRAE) were leukopenia (26.7%), neutropenia (20%) and pneumonia (6.7%). There was no surgical delays or unexpected surgical complications related to drug toxicity. Conclusions: The combination of sintilimab and chemotherapy shows an encouraging pCR rate and a favorable safety profile in this study, which indicated this treatment regimen may become an alternative option in the neoadjuvant treatment of resectable esophageal squamous cell carcinoma, especially for Chinese patients.