Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial

Abstract

In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50mg/m2 of paclitaxel and 25mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4Gy in 28 fractions), and toripalimab (240mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR]=13.73, 95% CI 4.43-42.54, P<0.0001) and PFS (HR=32.08, 95% CI 8.57-120.10, P<0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P=0.082) and better PFS (HR=0.43, 95% CI 0.19-0.93, P=0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P=0.036). The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis. National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.