3110 - Neoadjuvant Chemoradiotherapy plus Sequential Tislelizumab Followed by Surgery for Esophageal Carcinoma (CRISEC study): A Prospective, Single-Arm, Phase II Trial

J. Yang¹, Z. Zhang¹, B. Wu¹, C. Liu², Y. Qin¹, L. Wen¹, J. Wei¹, G. Xiao¹, S. Xing³, Y. Qu³, L. Huang³, X. Wang⁴, B. Wang⁵, Z. Zuo⁶, F. Cao⁶, K. Jiang³, and K. Yang¹; ¹Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ²Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ³Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ⁴Department of Thoracic Surgery, Subei Peoples Hospital, Yangzhou University, Wuhan, China, ⁵Department of Oncology, Northern Jiangsu Peoples Hospital, Yangzhou, China, ⁶Department of Oncology, Shiyan People’s Hospital, Hubei University of Medicine,, Shiyan, China

Purpose/Objective(s): The hypothesis is that adding tislelizumab sequentially after neoadjuvant chemoradiotherapy (NCRT) improved pathologic complete response (pCR, ypT0N0) rate after surgery in esophageal squamous cell carcinoma (ESCC). Materials/

Methods: Patients having locally resectable or potentially resectable thoracic ESCC with stage II-IVa (the 8^th edition of AJCC staging) were enrolled and allocated to neoadjuvant radiotherapy (41.4Gy in 23 fractions of 1.8 Gy per fraction, five fractions per week; Both elective nodal irradiation [ENI] and involved field irradiation [IFI] were allowed) with concurrent chemotherapy (albumin-bound paclitaxel, 50 to 100 mg/m², and carboplatin, area under the curve of 2 mg/ml/min, once weekly for five times) plus sequential tislelizumab (administered intravenously from the 1st to the 14th day after the end of radiotherapy at 200 mg every three weeks for three cycles) followed by esophagectomy with two-field lymphadenectomy. The primary endpoint was pCR rate. The second endpoints included safety, radical resection (R0) rate, major pathologic response (MPR) rate, progression-free survival (PFS) and overall survival (OS). Adverse events [AEs] were evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0.
Results: Twenty-four of thirty patients (80.0%) enrolled had clinical III-IVa stage. Twenty-eight patients received neoadjuvant tislelizumab, and 26 (92.9%) completed three doses per protocol. The median time from the end of chemoradiotherapy to the first dose of tislelizumab was 1 (range: 1–13) day. Twenty-four patients received planned surgery and gained R0 resection. pCR was achieved in 9 patients (37.5%) and MPR in 21 patients (87.5%). During NCRT, 30 patients (100%) developed grade 3 to 4 AEs, including lymphopenia (100.0%), neutropenia (53.3%), anemia (53.3%), leukopenia (50.0%), thrombocytopenia (20%) and pain (10%). During tislelizumab, 10 patients (35.7%) developed grade 3 to 4 AEs, including lymphopenia (32.1%), neutropenia (3.6%), leukopenia (3.6%) and thrombocytopenia (3.6%). Grade 5 hematemesis occurring in 2 patients during therapy were attributed to aorta invasion and tislelizumab-unrelated. Three patients (12.5%) developed grade 3 postoperative complications, including pulmonary infection (8.3%) and hoarseness (4.2%). The median follow-up period was 27.1 months for surviving patients. A total of four patients had tumor relapse after surgery and all were in the non-pCR group. Two-year OS and PFS rates for the entire cohort were 82.5% and 73.3%, respectively. Seven out of 13 patients (53.8%) receiving ENI had pCR compared to 2 out of 11 (18.2%) receiving IFI (p = 0.084).
Conclusion: Adding tislelizumab sequentially after NCRT followed by surgery in ESCC is safe and feasible. NCRT with ENI and tislelizumab is promising to improve tumor control of neoadjuvant therapy. Further study is warranted.