Neoadjuvant sintilimab combined with chemotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC): Preliminary results from a phase II study.

Abstract

e16008 Background: Although preoperative chemoradiotherapy is the standard of care for patients with resectable locally advanced esophageal cancer, prognosis still remains poor. Combining PD-1 blockade to chemotherapy has demonstrated significant clinical benefits in first line treatment of metastatic ESCC. Sintilimab, a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in metastatic ESCC. We aimed to assess the activity and safety profile of the combination of sintilimab with paclitaxel and cisplatin for neoadjuvant treatment of ESCC. Methods: In this ongoing, single-arm, phase II study, we recruited patients from the First Affiliated Hospital of Henan University of Technology in China with histopathologically diagnosed resectable ESCC who had clinical cT2-4/N1-3M0 (stage II-IVA). Patients were given 2 cycles of chemotherapy (nab-paclitaxel 260 mg/m2, d1 and cisplatin 75 mg/m2, d1-3) in combination with 2 cycles of sintilimab (200mg, iv, d1, q3w), followed by esophagectomy. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR). Results: Between Nov 2020 and Dec 2021, 15 patients were enrolled and commenced treatment. A total of 11 patients (75%) completed neoadjuvant and radical resection, 4 patients refused surgery. Six patients (54.5%) achieved major pathologic response (MPR), including five (45.5%) with a pathologic complete response (pCR) in primary tumor. According to RECIST v1.1, 1 of 8 patients (12.5%) achieved partial response (CR), 4 of 8 patients (50%) achieved partial response, and 3 of 8 patients (37.5%) achieved stable disease (SD). The objective response rate (ORR) and disease control rate (DCR) for 8 patients were 62.5% and 100%, respectively. The most frequent treatment-related adverse events (TRAE) included leukopenia (60%), nausea (40%) and diarrhea (20%). The grade 3 or 4 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: Neoadjuvant combination of sintilimab and chemotherapy is a safe and efficacious treatment option for patients with resectable ESCC, and 45.5% pCR rate is encouraging. Our clinical study is still enrolling, and the survival effects are under follow up. Clinical trial information: ChiCTR2000040345.