Immunotherapy in advanced esophageal squamous cell cancer: earlier or later?

Abstract

Background and objective: Several large-scale phase III clinical trials have confirmed the survival benefit of immunotherapy in patients with locally advanced or metastatic esophageal cancer. The aim of this study is to investigate whether early use of immunotherapy can improve long-term survival. Methods: Patients with locally advanced or metastatic esophageal squamous cell cancer (ESCC) diagnosed from January 2018 to December 2021were retrospectively analyzed. According to the time of immunotherapy, patients were divided into early immunotherapy group (EIT group, first-line immunotherapy ) and late immunotherapy group (LIT group, second-line immunotherapy) . A 1:1 propensity score matching (PSM) was applied to balance the observable potential confounding factors between the two groups. The primary outcome was overall survival (OS). Results: A total of 359 patients were enrolled, after propensity score matching, the clinical features were well balanced between two groups included 107 patients each. The median OS was 15.7 months (95%CI: 12.81-18.59) in the EIT group and 17.7 months (95%CI: 14.89-20.57) in the LIT group, respectively. (P=0.185, HR=1.25). The PFS1 of patients were 8.7 months (95%CI: 7.53-9.87) and 7.6 months (95%CI: 5.90-9.30),respectively, and the difference was statistically significant (P=0.032, HR=0.72). The PFS2 of patients were 12.97months (95%CI: 11.37-14.58) and 12.93 months (95%CI: 11.65-14.21), respectively, and the difference was statistically significant(P=0.045,HR=0.73). Subgroup analysis showed that male patients with middle thoracic esophageal cancer, younger than 65 years old, only one site of metastasis, only lymph node progression, no combined radiotherapy after progression and TP (paclitaxel plus platinum) regimen chemotherapy may have greater benefits. COX multivariate analysis showed that the EIT group and the differentiation degree of tumor had an impact on overall survival (P：0.03、0.04, HR: 0.73、0.70). Conclusions: For patients with locally advanced or metastatic advanced ESCC, earlyimmunotherapy can improve PFS without improving OS.