Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancy worldwide. The prognosis is poor with a five-year overall survival rate of 10 to 30 %. Randomized clinical trials have demonstrated that trimodality therapy (TMT), consisted of neoadjuvant concurrent chemoradiation (CCRT) and radical esophagectomy, improves the overall survival for patients with resectable locally advanced disease. Despite of the advancement, the outcome remained unsatisfactory with the median recurrence-free survival around 20 to 25 months and median overall survival around 30 months. It is known that the most important prognostic factor is whether a pathological complete response can be achieved after neoadjuvant CCRT. However, the use of new generation chemotherapeutic agent and epidermal growth factor inhibitors failed to significantly improve prognosis comparing to the standard platinum-based regimen. As a consequence, it is mandatory to develop new pharmacotherapeutic regimen for TMT.~In our previous prospective studies, we found higher levels of serum immune-related biomarkers, VEGF-A, TGF-β1, and soluble PD-L1, before neoadjuvant CCRT were independent associated with inferior overall survival and disease-free survival for locally advanced ESCC treated with neoadjuvant CCRT plus radical esophagectomy. Recent clinical trials have shown the efficacy of anti-PD-1 in recurrent/metastatic ESCC. Besides, preclinical and clinical studies suggested radiotherapy might induce local inflammatory stimulus for the immune modulating drug to boost the integrated response. In addition, preclinical study showed promising anti-cancer efficacy by combination of fractionated radiotherapy, anti-PD-L1 and/or anti-TIGIT immunotherapy. Though several prospective clinical trials have shown the feasibility, safety, and activity of adding anti-TIGIT therapy to anti-PD-L1 drug, and adding anti-PD-L1 therapy to chemotherapy in lung cancer, the safety and activity of combing anti-PD-1/PD-L1 to CCRT or TMT remained largely undetermined. In the present clinical trial, we plan to investigate whether incorporation of tiragolumab (Anti-TIGIT) and atezolizumab (Anti-PD-L1) into standard TMT will be safe while improve the pathological complete response rate. By the present research, we expect to develop a new TMT regimen for this poor prognostic disease.~This study is a single arm open labeled trial to evaluate the safety and pathological response of ESCC patients receiving neoadjuvant Paclitaxel/Cisplatin(TP)-CCRT plus Tiragolumab/Atezolizumab followed by radical esophagectomy. We design to enroll 32 patients to develop the preliminary evidence for incorporating tiragolumab/atezolizumab in locally advanced ESCC.
The prognosis of ESCC is poor with a five-year overall survival rate of 10 to 30 %. Randomized clinical trials have demonstrated that TMT, consisted of neoadjuvant concurrent CCRT and radical esophagectomy, improves the overall survival for patients with resectable locally advanced disease. As a consequence, it is mandatory to develop new pharmacotherapeutic regimen for TMT. In our previous prospective studies, we found higher levels of serum immune-related biomarkers, VEGF-A, TGF-β1, and soluble PD-L1, before neoadjuvant CCRT were independent associated with inferior overall survival and disease-free survival for locally advanced ESCC treated with neoadjuvant CCRT plus radical esophagectomy. In the present clinical trial, we plan to investigate whether incorporation of tiragolumab (Anti-TIGIT) and atezolizumab (Anti-PD-L1) into standard TMT will be safe while improve the pathological complete response rate. By the present research, we expect to develop a new TMT regimen for this poor prognostic disease.