Total Neoadjuvant Therapy Combined with Adebrelimab in Locally Advanced Resectable ESCC

Esophageal cancer is a malignant tumor with high incidence rate and mortality in China. According to the data of the World Health Organization, 324000 new cases and 301000 deaths of esophageal cancer will occur in China in 2020, accounting for 53.70% and 55.35% of the global incidence and death of esophageal cancer respectively. Surgery is the main method for locally advanced resectable esophageal cancer, combined with chemoradiotherapy(CRT), in order to achieve curative resection. However, after neoadjuvant chemoradiotherapy and surgery, 36-50% of patients still experience recurrence or metastasis, and the prognosis for early recurrence is worse. Adjuvant chemotherapy plays a particularly beneficial role in terms of disease-free survival(DFS) in patients who did not receive neoadjuvant therapy and patients with pathologic lymph-node-positive disease. however, less than 50% of eligible patients receive their scheduled adjuvant chemotherapy due to delays, treatment compliance, and postoperative complications. Among patients with resected esophageal cancer who had received neoadjuvant CRT, DFS was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. Total neoadjuvant therapy (TNT), attempts to deliver both systemic chemotherapy and neoadjuvant CRT prior to surgery, which may become a new treatment direction for patients with locally advanced resectable esophageal cancer. Ongoing progress in all treatment modalities involved in TNT holds the promise to enhance further the outcomes of patients with esophageal cancer. Immunotherapy, as a breakthrough therapy in the systemic treatment of advanced esophageal cancer, has become an indispensable component of the exploration of TNT model. Currently, several prospective exploratory studies suggest that immunotherapy combined with TNT can improve the pCR rate of esophageal cancer patients, achieving good short-term efficacy and tolerable safety. However, further exploration is needed for the combination of immunotherapy and TNT. This study first explores the efficacy and safety of two types of total neoadjuvant therapy in phase II: the combination of adebrelimab and chemotherapy followed by chemoradiotherapy, or the combination of adebrelimab and chemotherapy after chemoradiotherapy. A more promising treatment plan will be selected for a phase III randomized controlled trial and confirm the superiority of adebrelimab combined with TNT over neoadjuvant CRT in terms of pathological complete response overall survival in patients with locally advanced resectable esophageal cancer.