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Neoadjuvant toripalimab plus concurrent chemoradiotherapy for locally advanced adenocarcinoma of the esophagogastric junction: a phase II trial

Year: 2026

Type: article

Abstract: Neoadjuvant chemoradiotherapy plus surgery is for the treatment of locally advanced adenocarcinoma of the esophagogastric junction (AEG), yet pathological response remains suboptimal. Given the potential synergy between PD-1 blockade and radiotherapy in modulating the tumor immune microenvironment, we hypothesized that adding toripalimab, a PD-1 inhibitor, to neoadjuvant chemoradiotherapy could improve tumor response. We enrolled cT3-T4/N + M0 AEG patients in this prospective, single-arm, phase II trial. Patients received neoadjuvant radiotherapy (50 Gy/45 Gy/25 f), with 5 cycles of weekly chemotherapy concurrently and 4 cycles of toripalimab, followed by radical surgery and adjuvant chemoimmunotherapy. The primary endpoint was the major pathological response (MPR) rate; the secondary endpoints included the pathological complete response (pCR) rate, R0 resection rate, disease-free survival (DFS), overall survival (OS), event-free survival (EFS) and safety, with exploratory analyses of immune correlates including the tertiary lymphoid structure (TLS). Between September 1, 2019, and April 30, 2024, 40 patients were enrolled. Thirty-one patients underwent radical surgery. In the surgery population, R0 resection rate was 100%, 24 patients (77.4%) achieved an MPR, and the pCR rate was 41.9%. In terms of safety, only one case of ≥ grade 4 treatment-related toxicity and one case of ≥ grade 3 surgical complication were reported. Notably, pCR patients were more likely to have detectable TLSs ( p = 0.047). During a median follow-up period of 54.4 months for OS and 51.6 months for DFS, the surgery set had 2-year and 4-year OS rates of 93.5% and 86.6%, versus 85.0% and 71.5% in the whole population. The 2-year and 4-year DFS rates of the surgery cohort were 83.9% and 80.4% respectively. Neoadjuvant toripalimab combined with chemoradiotherapy demonstrates promising efficacy and manageable toxicity in locally advanced AEG, with a notable association between TLS and pathological response. This study was registered at ClinicalTrials.gov as NCT04061928 in August 2019.

Source: BMC Medicine

DOI: 10.1186/s12916-026-05337-2