Comparing toripalimab combined with chemoradiotherapy versus chemoradiotherapy alone for locally advanced esophageal squamous cell carcinoma: A multicenter, open-label, randomized phase II clinical trial.

4079 Background: Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype in Asia, representing approximately 90% of all esophageal cancer cases. Despite definitive chemoradiotherapy (CRT) being the standard treatment for unresectable locally advanced ESCC, the prognosis remains poor. The introduction of PD-1 inhibitors has shown significant improvement in survival outcomes for advanced ESCC. This study aims to evaluate the efficacy and safety of combining induction and consolidation toripalimab (a PD-1 inhibitor) with CRT in patients with locally advanced ESCC (Clinical trial information: NCT04084158). Methods: Patients aged 18-75 years with unresectable, locally advanced ESCC and an ECOG performance status of 0-1 were eligible. Participants were randomly assigned (1:1) to either two cycles of toripalimab (3mg/kg q2ws) followed by concurrent CRT with 50.4Gy+weekly paclitaxel and carboplatin (TC), TC consolidation, and toripalimab (study arm), or standard CRT alone (control arm). The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and objective response rate (ORR). Results: Between September 2019 and July 2020, 46 ESCC patients (40 males) were screened for eligibility across four participating centers in China. Forty-four patients were eligible for survival analysis, all with histopathologically confirmed ESCC. Median ages were 64 years (range 49-75) in the study arm and 61 years (range 47-74) in the control arm, with similar clinical AJCC stages. As of the February 1, 2024 cutoff, the median follow-up was 50.6 months. Median PFS was 10.0 months in the study arm and 17.8 months in the control arm (HR: 1.567, 95% CI: 0.755-3.251, p=0.228). Median OS was 23.7 months and 25.9 months, respectively (HR: 1.140, 95% CI: 0.536-2.427, p=0.733). ORR rates were 64% and 86% (p=0.164), respectively. The incidence of grade 3 or worse treatment-related adverse events was similar between groups, with the most common adverse event being lymphopenia. Conclusions: Our findings indicate no significant benefit in adding induction and consolidation immunotherapy to CRT for treating locally advanced ESCC. However, the combination of radiotherapy and immunotherapy warrants further exploration. Ongoing analyses of biomarker correlates of response and survival will provide additional insights. Clinical trial information: NCT04084158 .