Chemotherapy plus camrelizumab versus chemotherapy alone as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (ESCORT-NEO): A multi-center, randomized phase III trial.
Yin Li, Jianjun Qin, Liyan Xue, Anlin Hao, Tao Jiang, Shuoyan Liu, Hongjing Jiang, Mingqiang Kang, Hecheng Li, Hui Tian, Junke Fu, Jianqun Ma, Maoyong Fu, Yongtao Han, Longqi Chen, Lijie Tan, Tianyang Dai, Yongde Liao, Weiguo Zhang, Bin Li
Abstract
LBA244 Background: Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is the standard of care for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, recurrence post-surgery remains a concern. Recent single-arm studies with neoadjuvant camrelizumab plus chemotherapy showed promising results. This multicenter, randomized, open-label, phase III study aims to evaluate the role of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, versus neoadjuvant chemotherapy alone for resectable LA-ESCC. Methods: Patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified according to clinical stage (I/II, III, or IVa) and randomized (1:1:1) to three groups for two 3-week cycles of neoadjuvant therapy. Group A received camrelizumab, albumin-bound paclitaxel and cisplatin; group B used camrelizumab, paclitaxel and cisplatin; group C received paclitaxel and cisplatin. Surgery was planned 4-6 weeks post-neoadjuvant therapy. Postoperative adjuvant camrelizumab every 3 weeks was given to groups A and B for up to 15 cycles. The co-primary endpoints were pathological complete response (pCR) rate, assessed by an independent blinded pathological committee, and event-free survival, evaluated by investigators per RECIST 1.1. The overall type I error was controlled at a one-sided 0.025 across the primary endpoints using a graphical method. Results: Between April, 2021, and August, 2023, we enrolled 391 patients: group A (n = 132), group B (n = 130), and group C (n = 129). 106 (27.1%), 279 (71.4%), 6 (1.5%) patients were in clinical stage I/II, III, and IVa. Tumors were located in the upper, middle, and lower thoracic esophagus for 41 (10.5%), 201 (51.4%), and 149 (38.1%) patients. 128 (97.0%), 125 (96.2%), and 122 (94.6%) patients from groups A, B, and C completed two cycles of neoadjuvant therapy, and 114 (86.4%), 116 (89.2%), and 103 (79.8%) underwent surgery. In the intention-to-treat population, the pCR rate was significantly higher in groups A (28.0%) and B (15.4%) compared to group C (4.7%) (group A vs. C: difference, 23.5%, 95%CI, 15.1-32.0; OR, 8.11, 95%CI, 3.28-20.06; two-sided P < 0.0001; group B vs. C: difference, 10.9%, 95%CI, 3.7-18.1; OR, 3.81, 95%CI, 1.48-9.80; two-sided P = 0.0034); major pathologic response rates were 59.1%, 36.2%, 20.9% for groups A, B and C. In the surgical set, the R0 resection rate was 99.1%, 95.7% and 92.2% for groups A, B and C, and the incidence of postoperative complications was 34.2%, 38.8% and 32.0%. During neoadjuvant treatment, the incidence of grade ≥3 treatment-related adverse events was 34.1%, 28.5% and 28.8%. Conclusions: In resectable LA-ESCC patients, neoadjuvant camrelizumab with chemotherapy showed superior pCR and a tolerable safety profile compared to neoadjuvant chemotherapy alone. Clinical trial information: ChiCTR2000040034 .