Induction Therapy of Tislelizumab Combined with Cisplatin and 5-Fluorouracil and Subsequent Conversion Surgery in Patients with Unresectable Advanced Esophageal Squamous Cell Carcinoma: A Phase 2, Single Center Study.

BACKGROUND

This study reported the safety and efficacy of a phase 2, open-label, single-arm, exploratory clinical trial of induction immunochemotherapy in patients with initially unresectable advanced esophageal squamous cell carcinoma (ESCC).

PATIENTS AND METHODS

Patients underwent three cycles of induction therapy with tislelizumab, cisplatin, and 5-fluorouracil. The primary endpoints were the safety, major pathological response (MPR), and pathological complete response (pCR). Secondary endpoints included the R0 resection rate, disease-free survival (DFS), and overall survival (OS). Genomic data and immune microenvironment data were analyzed exploratively.

RESULTS

The treatment was safe, with a grade 3 or higher adverse event rate of 14.9% (7/47). Of the total 47 patients enrolled in the study, 19 (40.4%) achieved MPR, 12 (25.5%) achieved pCR, 4 (8.5%) achieved complete clinical response (cCR) and declined surgery, and 23 (48.94%) underwent successful resection. Median follow-up was 18 months, with a median DFS of 24 months, a median OS of 36 months. A high tumor mutation burden was associated with a better prognosis for patients who underwent surgery. Patients who achieved pCR had higher levels of immune cell infiltration and a greater proportion and concentration of tertiary lymphoid structures compared with those who experienced a major pathological response.

CONCLUSIONS

Tislelizumab combined with chemotherapy is effective for ESCC, yielding high cCR, pCR, surgical conversion, and R0 resection rates, and tolerable adverse events.

TRIAL REGISTRATION

NCT05469061.