Esophageal cancer is one of the most common malignant tumors in the gastrointestinal tract. As one of the regions with the highest risk of esophageal cancer in the world, China accounts for about 40% of the new cases in the world every year. 53.7% of the total, and the number of deaths accounts for about 55.7% of the global total. As a tumor type with “Chinese characteristics”, there is a huge difference in the distribution of pathological types of esophageal cancer between East and West. More than 90% of esophageal cancers are esophageal squamous cell carcinomas. Because many patients are diagnosed with advanced disease, esophageal squamous cell carcinoma has a poor overall prognosis, challenging disease management, and a large unmet clinical need.
Recently, RATIONALE 306, a global phase 3 clinical trial of tislelizumab combined with chemotherapy in patients with first-line advanced or metastatic esophageal squamous cell carcinoma, met the primary endpoint of overall survival (OS), which means that Therefore, patients with advanced esophageal squamous cell carcinoma are expected to usher in new treatment options.
RATIONALE 306 (NCT03783442) is a randomized, placebo-controlled, double-blind, large, global Phase 3 study evaluating tislelizumab plus chemotherapy versus placebo plus chemotherapy as Efficacy and safety of first-line treatment regimens in patients with advanced or metastatic esophageal squamous cell carcinoma. The primary endpoint of the trial was overall survival (OS). Secondary endpoints included progression-free survival, overall response rate and duration of response, health-related quality of life measures, and safety as assessed according to RECIST version 1.1.
The study, led by Chinese researchers, enrolled a total of 649 patients in multiple research centers in Asia Pacific, Europe and North America, of which 55% were from mainland China, 25% from Europe and the United States, and 20% from Japan. Korea and other countries and regions. This patient distribution is in line with the pathogenesis of esophageal squamous cell carcinoma, which is of great significance for understanding the value of immunotherapy for the diagnosis and treatment of esophageal squamous cell carcinoma worldwide, and analyzing the efficacy and advantages of immunotherapy for people in different regions. It is worth mentioning that based on the differences in the clinical practice of experts in esophageal cancer treatment in Asia and Europe and the United States, the choice of chemotherapy regimens in the RATIONALE 306 study is also more inclusive. The efficacy data of various chemotherapy regimens combined with immunotherapy will further clarify the esophagus. Combination therapy strategies for squamous cell carcinoma provide reference for clinical application.
Tislelizumab has been officially approved by the China National Medical Products Administration (NMPA) for the treatment of locally advanced or metastatic esophagus that has progressed or is intolerable after first-line standard chemotherapy patients with squamous cell carcinoma. At present, tislelizumab has achieved eight indications in China. As a PD-1 monoclonal antibody (tumor immunotherapy drug) with special genetic engineering of the Fc segment, the unique structural optimization of tislelizumab in preclinical studies enables it to avoid antibody-dependent cells Mediated phagocytosis (ADCP), Fab segment completely and persistently block the combination of PD-1 and PD-L1, long half-life, strong anti-tumor activity and other four major pharmaceutical advantages. These advantages not only lay the foundation for the success of the previous series of studies, but also provide directions for subsequent clinical exploration and application.
(Pan Jiayi)