Phase II trial reports response with neoadjuvant toripalimab for junctional cancer

Neoadjuvant chemoradiotherapy followed by surgery is used for locally advanced adenocarcinoma of the esophagogastric junction (AEG), but pathological response remains suboptimal. This prospective, single-arm phase II trial enrolled 40 patients with cT3–T4/N+ M0 disease between September 2019 and April 2024. Treatment comprised radiotherapy with concurrent weekly chemotherapy and four cycles of the PD-1 inhibitor toripalimab, followed by surgery and adjuvant chemoimmunotherapy. Major pathological response was the primary endpoint.

Thirty-one patients underwent radical surgery. In this group, the R0 resection rate was 100%; 24 patients (77.4%) achieved a major pathological response, and 41.9% had a pathological complete response. One patient had a treatment-related toxicity of grade 4 or higher, and one had a surgical complication of grade 3 or higher. Patients with pathological complete response were more likely to have detectable tertiary lymphoid structures (p=0.047). Median follow-up was 54.4 months for overall survival and 51.6 months for disease-free survival; the surgery cohort’s 4-year overall and disease-free survival rates were 86.6% and 80.4%, respectively.

The findings are promising but come from a small, non-randomized phase II study; nine enrolled patients did not undergo surgery. The results do not establish that adding toripalimab improves outcomes compared with chemoradiotherapy alone, and the association with tertiary lymphoid structures is exploratory.