1405P - Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for esophageal squamous cell carcinoma (EC-CRT-001 phase II trial)

Background

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 esophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses.

Methods

This was a single-arm, phase II trial in which 42 patients with unresectable stage I–IVA ESCC, were treated with chemotherapy (weekly 50 mg/m² of paclitaxel and 25 mg/m² of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). Three-year overall survival (OS) and progression-free survival (PFS) were evaluated. Exploratory objectives included recurrence pattern, the association between immune-related adverse events (irAEs) and efficacy, and potential predictors for irAEs.

Results

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 clinical complete response (CR) demonstrated significantly inferior OS (HR=13.7, 95% CI 4.4–42.5, P<0.001) as well as PFS (HR=32.1, 95% CI 8.6–120.1, P<0.001). Twenty-three of 42 patients (54.8%) experienced disease recurrence. Recurrences were much earlier and more frequently in non-CR group versus CR group. Patients who had irAEs showed significantly higher CR rate (72.4% vs. 38.5%, P=0.047) and better PFS (HR=0.4, 95% CI 0.2–0.9, P=0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P=0.018).

Conclusions

The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs might predict a more favorable prognosis.

Clinical trial identification

NCT04005170.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China; Beijing Xisike Clinical Oncology Research Foundation; Sci-Tech Project Foundation of Guangzhou.

Disclosure

All authors have declared no conflicts of interest.