Neoadjuvant Chemoradiotherapy Combined with Nimotuzumab and Camrelizumab in Initially Inoperable Patients with Locally Advanced Esophageal Cancer: A Prospective, One-Arm, Phase II Study

Abstract

The neoadjuvant chemoradiotherapy combined with surgery has become the standard treatment model for operable locally advanced esophageal cancer. This present study was aimed to explore the feasibility and safety of neoadjuvant chemoradiotherapy combined with nimotuzumab and camrelizumab in initially inoperable patients with locally advanced esophageal cancer (NCT0535168). Patients with initially inoperable locally advanced esophageal cancer were enrolled. All patients were supposed to receive neoadjuvant chemoradiotherapy (40.85-41.4Gy/19-23f plus albumin paclitaxel (0.05g qw) and cisplatin (30mg qw)). The nimotuzumab (EGFR antibody targeting extracellular domain) was administrated 200mg weekly and the camrelizumab was taken 200mg every 3 weeks. The primary endpoints were safety and the surgical conversion rate. The second endpoints were pathological response, 1, 2 and 3-years disease free survival, and alteration of the immune microenvironment after neoadjuvant therapy. From December 2021 to now, 20 initially inoperable patients with locally advanced esophageal cancer were enrolled in this study, including 16 males and 4 females. The median age was 65 years. 19 patients were squamous cell carcinoma, and 1 patient was adenocarcinoma. The surgical conversion rate was 70% (14/20). The pathological complete response rate was 35.7% (5/14). The main AEs were radiation esophagitis and hematological toxicity. 4 patients developed over Grade III myelosuppression (3 for Grade Ⅲ (15%) and 1 for Grade Ⅳ (5%). 1(5%) patient developed Grade III atopic dermatitis. No patients died or with disease progression in patients who underwent surgery up to now. Compare to pre-treatment baseline, CD8+T cell and IFN-γ were significantly increased, IL-8 was significantly decreased in peripheral blood after neoadjuvant therapy. The neoadjuvant chemoradiotherapy combined with nimotuzumab and camrelizumab was with high surgical conversion rate and acceptable safety in initially inoperable patients with locally advanced esophageal cancer.