Neoadjuvant toripalimab plus chemotherapy followed by concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (GASTO 1071).

4077 Background: The combination of immune checkpoint inhibitor and concurrent chemoradiotherapy (CCRT) has been under investigation in patients with unresectable, locally advanced esophageal squamous cell carcinoma (ESCC). We explored the efficacy and safety of neoadjuvant toripalimab plus chemotherapy followed by CCRT in patients with locally advanced 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). All patients were aged 18–80 years with an Eastern Cooperative Oncology Group performance status of 0–1. Patients in both cohorts received neoadjuvant therapy comprised of paclitaxel-albumin, nedaplatin and toripalimab 240 mg every 3 weeks, for 2 cycles, followed by CCRT (total dose 60Gy in cohort A, 50 Gy in cohort B, combined with oral capecitabine). The primary endpoint was progression-free survival (PFS) from enrollment. The trial is registered with ClinicalTrials.gov, NCT04844385. Results: Between February 26, 2021, and June 20, 2023, a total of 63 patients were enrolled in cohort A (54 men 85.7%; median interquartile range age, 63 58-65 years; 57 90.5% patients had stage III to IVB disease), and 61 patients were enrolled in cohort B (43 men 70.5%; median interquartile range age, 65 57-69 years; 52 85.2% patients had stage III to IVB disease). The objective response rate assessed 2 months after CCRT was 93.7% in cohort A and 93.4% in cohort B. At data cutoff (January 31, 2024), the median (range) follow-up duration was 31.3 (2.5-47.1) months in cohort A, and 17.0 (5.7-38.7) months in cohort B. The 12-month and 18-month PFS rates were 78.3%, 64.4% in cohort A, and 75.7%, 63.6% in cohort B. Median PFS was not reached in either cohort. Locoregional recurrence was observed in 19.0% (12/63) of patients in cohort A, and 24.6% (15/61) of patients in cohort B. Distant metastasis was observed in 12.7% (8/63) of patients in cohort A, and 3.3% (2/61) of patients in cohort B. Grade 3 and 5 pneumonitis occurred in 3.2% (2/63) and 1.6% (1/63) in cohort A, respectively, while no grade 3+ pneumonitis occurred in cohort B. Treatment-related esophageal fistula occurred in 1.6% (1/63) in cohort A and 1.6% (1/61) in cohort B. Conclusions: Neoadjuvant toripalimab plus chemotherapy followed by definitive CCRT demonstrated promising efficacy and acceptable toxicity in patients with locally advanced ESCC. Further study is warranted to confirm this conclusion. Clinical trial information: NCT04844385 .