Neoadjuvant tislelizumab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Interim analysis of a phase 2 study.

person Na Zhuo Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China info_outline Na Zhuo, Wei Qiu, Jia He, Li Li, Qiang Wang, Shuangni Yu, Wei Liu, Lin Zhao, Chunmei Bai

Authors person Na Zhuo Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China info_outline Na Zhuo, Wei Qiu, Jia He, Li Li, Qiang Wang, Shuangni Yu, Wei Liu, Lin Zhao, Chunmei Bai Organizations Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China, Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China, Department of Thoracic Surgery, Peking Union Medical College Hospital,CAMS & PUMC, Beijing, China, Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China, Department of Pathology, Peking Union Medical College Hospital, Beijing, China, Department of radiology, Peking Union Medical College Hospital, Beijing, China, Department of Medical Oncology，Peking Union Medical College Hospital, Beijing, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Beigene Pharmaceutical (Shanghai) Co. Ltd, National High level Hospital Clinical Research Funding 2022-PUMCH-A-215 Background: Esophageal cancer (EC), as the sixth most frequently diagnosed cancer and the fourth leading cause of cancer death, poses a major health threat in China. Neoadjuvant treatment is recommended for resectable diseases with high recurrent risks; however, benefits with platinum-doublet chemotherapy are modest. Although the addition of tislelizumab, a anti-PD-1 antibody to chemotherapy has shown survival benefit in unresectable or metastatic EC, data are lacking to support such combination as a neoadjuvant modality. Here, we report the interim analysis of efficacy and safety of a prospective, phase 2 clinical trial evaluating tislelizumab plus chemotherapy as neoadjuvant treatment for locally advanced ESCC. Methods: Adults with clinical stage II-IVA (T3-T4 and/or node positive), potentially resectable ESCC, ECOG PS 0-1, and no known PD-1 expression were enrolled to receive tislelizumab (200mg) plus chemotherapy (docetaxel 75mg/m 2 plus cisplatin 75mg/m 2 or carboplatin AUC = 5 if CCr < 60ml/min) every 3 weeks for 4 cycles. Adjuvant tislelizumab up to 9 months were optional according to patients’ will. The primary endpoint was pathological complete response (pCR). Secondary endpoints include R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy. Results: Between November 11, 2020 and Feburary 10, 2023, 28 patients with clinical stage III (n = 13) or IVA (n = 15) diseases were enrolled. 27 completed neoadjuvant treatment and 5 withdrew early because of disease progression (n = 2), serious AEs (n = 2) and bronchoesophageal fistula (n = 1). 21 patients underwent McKeown MIE and 20 (95.2%) acheived R0 resection. One patient was awaiting surgery. pCR (ypT0N0) was achieved in 33.3% (7/21) patients. According to the CAP tumor regression grading system, 3 (14.3%) cases were categorized as grade 1, 7(33.3%) were categorized as grade 2 and 4 (19%) were categorized as grade 3 in primary tumor. Most treatment related AEs (TRAEs) during neoadjuvant setting were mainly of grade 1 or 2. Grade 3 or 4 TRAEs occurred in 37.0% patients (10/27) and 14.8% (4/27) was considered immune-related. Surgical complications of any grade occurred in 4 patients (19.0%), 3 of which were grade 3. No grade 5 events were noted. 14 (66.7%) patients were able to continue adjuvant tislelizumab after surgery. Conclusions: Neoadjuvant tislelizumab plus chemotherapy has achieved encouraging pCR rate and tolerable safety activity in this study. Clinical trial information: ChiCTR2100043772.

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