Neoadjuvant concurrent chemoradiotherapy with surgery is the standard treatment for esophageal squamous cell carcinoma (ESCC) in NCCN guidelines. But many patients refused or abandon radiotherapy because of the intolerable adverse effects. We designed a single-arm, open-label, phase II trial of pembrolizumab plus paclitaxel, cisplatin followed by Da Vinci robot surgery for locally advanced (stage III) ESCC. The purpose is to observe and evaluate the efficacy and safety.
The enrolled subjects are the locally advanced and resectable (stage Ⅲ，8th, AJCC) ESCC patients, who will receive pembrolizumab (200mg, IV, D1, Q3W for 3 cycles), paclitaxel (135mg/m2, IV, D2, Q3W for 3 cycles) ，and cisplatin (20mg/m2, IV, D2-4, Q3W for 3 cycles), then will undergo Da Vinci robot-assisted McKeown surgery within 4-6 weeks after neoadjuvant treatment. If the pathology result is not a complete response, pembrolizumab alone as adjuvant therapy should be continued for at least 6 cycles with the same usage as before. Primary endpoints: major pathological response (MPR) rate; the safety. Secondary endpoints: pathological complete response (pCR) rate, objective response rate (ORR); 1, 3, 5-years OS and DFS, R0 resection rate and 30-day perioperative complications. Quality of life (EORTC QLQ-C30, OES18) and nutrition assessment (PG-SGA score).
This trial has recruited 42 subjects (50 in plan), of which 29 have finished robot surgery. The results confirm that this new treatment is safe (no adverse events of grade 3 or higher), and did not cause a delay in surgery. Patients' nutritional status and QOL improved significantly. R0 resection rate is 100%, with MPR 21/29 (72.4%), pCR 12/29 (41.4%), and ORR 28/29 (96.6%). No perioperative death has occurred so far.
Pembrolizumab combined with paclitaxel and cisplatin as a neoadjuvant therapy was associated with few side effects, did not delay surgery, and induced a major pathological response in 72.4% of resected ESCC tumors. It may be better than the neoadjuvant concurrent chemoradiation recommended by NCCN guidelines.
Clinical trial identification
NCT 04389177, date of registration: 15 May 2020.
All authors have declared no conflicts of interest.