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.