Safety and efficacy of neoadjuvant toripalimab plus chemotherapy followed by chemoradiotherapy for locally advanced esophageal squamous cell carcinoma in China (GASTO 1071): a non-randomised, two-cohort, phase 2 trial.

Background: We aimed to explore the efficacy and safety of neoadjuvant toripalimab plus chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). Methods: This phase II, non-randomized, 2-cohort study enrolled patients with unresectable, stage T1-4N0-3M0-1 ESCC (M1 only includes patients with lymph node metastasis in the supraclavicular region). Patients received neoadjuvant therapy comprised of albumin-bound paclitaxel, nedaplatin and toripalimab every 3 weeks, for 2 cycles, followed by CCRT (total dose 60Gy in cohort A, 50Gy in cohort B, combined with oral capecitabine). The primary endpoint was progression-free survival (PFS). The trial is registered with ClinicalTrials.gov, NCT04844385. Findings: Between February 26, 2021 and June 20, 2023, 124 patients were enrolled, and 118 (95.2%) patients completed treatment. The objective response rate to neoadjuvant chemo-immunotherapy was 91.9% overall, and was 93.7% in cohort A-60Gy and 93.4% in cohort B-50Gy after CCRT. With a median follow-up of 30.8 months, the 18-month PFS rates were 65.0% (95% CI, 53.9-78.3%) in cohort A-60Gy and 65.1% (95% CI, 53.7-78.8%) in cohort B-50Gy. Grade (G) 3 and G5 pneumonitis occurred in two (3.2%) and one patient (1.6%) in cohort A-60Gy, respectively, with no ≥G3 pneumonitis in cohort B-50Gy. Improvements on patient reported outcomes from baseline to 12 months post-CCRT were observed overall. Interpretation: Neoadjuvant chemo-immunotherapy, radiotherapy and concurrent capecitabine achieved promising efficacy in locally advanced ESCC. Further investigation is warranted. Funding: None.