Neoadjuvant chemoradiotherapy plus sequential tislelizumab followed by surgery for esophageal carcinoma (CRISEC study): A single-arm, bicentric, phase 2 trial

Abstract

Background and purpose

To explore the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) plus sequential tislelizumab followed by surgery for esophageal squamous cell carcinoma (ESCC).

Materials and methods

This single-arm, bicentric, phase 2 trial enrolled patients with resectable or potentially resectable thoracic ESCC to receive neoadjuvant radiotherapy (41.4 Gy in 23 fractions) with concurrent chemotherapy (albumin-bound paclitaxel, 50–100 mg/m², and carboplatin, area under the curve of 2 mg/ml/min, once weekly, five times) plus sequential tislelizumab (200 mg Q3W, three cycles) followed by surgery. The primary endpoint was pathologic complete response (pCR) rate. The secondary endpoints included safety, R0 resection rate, major pathologic response (MPR) rate, disease-free survival (DFS), and overall survival (OS).

Results

Of the 30 patients enrolled from January 2021 to October 2022, 24 (80.0 %) completed planned surgery and gained R0 resection (100 %). Among the 24 patients, nine (37.5 %) achieved pCR and 21 (87.5 %) achieved MPR. Ten patients (35.7 %) developed grade 3–4 toxicities during tislelizumab therapy, including lymphopenia (32.1 %), neutropenia (3.6 %), and thrombocytopenia (3.6 %). Grade 5 hematemesis occurred in two patients and both were attributed to aortic invasion. Three patients (12.5 %) developed grade 3 postoperative complications, including pulmonary infection (8.3 %) and hoarseness (4.2 %). After a median follow-up of 35.4 months, the 2-year OS and DFS rates were 83.3 % and 79.2 %, respectively.

Conclusion

Sequential tislelizumab after NCRT in ESCC is safe and feasible. Further study is warranted to validate the efficacy of this combination mode.