Neoadjuvant Chemoradiotherapy Combined With PD-1 Antibody in Locally Advanced Esophageal Cancer

Overview

This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy with concurrent Chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative Teripalimab and other immune checkpoint therapy in esophageal cancer treatment.

Esophageal cancer ranks the eighth most common cancer in Worldwide. And the third among men and the fifth among women in China, among which esophageal squamous cell carcinoma accounts for about 90%. Neoadjuvant therapy for esophageal cancer is increasingly supported by evidence. However, the results of neoadjuvant therapy are not completely consistent. Most studies of neoadjuvant treatment data for esophageal cancer were obtained from western populations, where esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were more common and the sample size was relatively small. According to the meta-analysis of the reported results of randomized controlled trials, concurrent chemoradiotherapy has a higher pathological complete response rate than chemotherapy alone as neoadjuvant therapy. However, the 3-year survival rate of neoadjuvant chemoradiotherapy only showed an advantage in patients with squamous cell carcinoma (56.8%vs42.8%), but no significant difference in patients with adenocarcinoma (46.3%vs41.0%). Pathological complete remission rate of esophageal cancer after neoadjuvant chemotherapy is relatively low. It can be seen that positive expression of programmed death ligand-1 is more common in Esophageal squamous cell carcinoma, and programmed death ligand-1 tends to be overexpressed compared with adjacent normal epithelial cells. The later the T-stage of the tumor, the higher the positive expression rate. In addition, programmed death ligand-1 expression is significantly correlated with lymphatic metastasis. Therefore, programmed death ligand-1 expression can promote tumor progression. The recurrence rate of patients with programmed death ligand-1 expression is higher after treatment, and the postoperative complete pathological remission rate is lower in programmed death ligand-1 positive patients. In addition, positive programmed death ligand-1 expression also reduces the sensitivity of radiotherapy, which may be contributing factors to poor prognosis of patients with positive pd-l1 expression. It is worth mentioning that clinical treatment will affect the expression level of programmed death ligand-1 in esophageal cancer tissues. Neoadjuvant concurrent chemoradiotherapy can up-regulate the expression of programmed death ligand-1 in ESCC significantly, while neoadjuvant chemotherapy can down-regulate the expression of pd-L1. However, radiotherapy can up-regulate the expression level of programmed death ligand-1 in esophageal cancer cells, which is positively correlated with radiation dose, and the combination of anti-pd-L1 therapy and radiotherapy can lead to increased tumor cell lysis, which also indicates the importance of comprehensive treatment of tumor. There are relatively few studies on the treatment of esophageal cancer with pd-1 / pd-L1 inhibitors. Keynote-059 enrolled 259 patients with advanced gastric or gastroesophageal junction cancer in the phase II clinical trial of Pembrolizumab, with an objective response rate of 11.6%, complete response rate of 2.3%, and median response duration of 8.4 months. Persistent objective response rates were observed in both programmed death ligand-1 positive and negative patients, and adverse reactions were tolerable. The efficacy and safety of anti-pd-1 / pd-L1 therapy in the treatment of esophageal cancer still need a lot of clinical studies to further confirm. This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative Teripalimab and other immune checkpoint therapy in esophageal cancer.

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Central Contacts