A Phase 1b Clinical Trial of Neoadjuvant Radio-immunotherapy for Esophageal Squamous Cell Cancer

Abstract

BackgroundNeoadjuvant chemoradiotherapy is the recommended treatment for patients with resectable esophageal cancer; however, it is associated with a higher incidence of adverse effects. Given the efficacy of immunotherapy, we propose a chemotherapy-free regimen of neoadjuvant radio-immunotherapy (NRIT) to balance therapeutic efficacy and potential side effects or overtreatment. MethodsIn this phase Ib clinical trial, we assessed the safety and efficacy of NRIT in esophageal squamous cell cancer (ESCC). The enrolled patients received 41.4 Gy of radiation and four cycles of 240 mg of Toripalimab injection before surgery. The primary endpoint was treatment-related adverse events (TRAEs), and the secondary endpoints included pathological complete response (pCR) and major pathological response (MPR). Immunohistochemistry and multiplex immunofluorescence staining were utilized to evaluate the tumor microenvironments before and after neoadjuvant treatment. FindingsOut of the 22 patients enrolled, 19 underwent R0 surgery. One patient discontinued neoadjuvant immune therapy due to grade 3 TRAEs, and three patients did not undergo surgery due to tumor progression or side effects. Another three patients experienced serious complications shortly after surgery. Upon pathological evaluation, the pCR and MPR rates were 47.4% and 68.4%, respectively. ConclusionThe NRIT regimen is safe and feasible for patients with ESCC.