PMID- 34926667 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220830 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 9 IP - 21 DP - 2021 Nov TI - Neoadjuvant sintilimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, single-center, phase 2 trial (ESONICT-1). PG - 1623 LID - 10.21037/atm-21-5381 [doi] LID - 1623 AB - BACKGROUND: To investigate the safety and feasibility of combining neoadjuvant sintilimab (Innovent Biologics, Suzhou, China) and chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: The study was an investigator-initiated, open-label, non-randomized, single-arm, single-center phase 2 trial. Patients aged between 18 to 75 years with locally advanced ESCC were eligible for neoadjuvant immunochemotherapy (nICT). The nICT included cisplatin (60 mg/m(2)) on day 1, albumin-bound paclitaxel (125 mg/m(2)) on days 1 and 8, and sintilimab (200 mg) on day 1 of each 21-day cycle. Clinical evaluation was conducted after 2 cycles of nICT. Within 4-6 weeks after nICT, patients underwent esophagectomy. The primary end points were pathological complete response (pCR) and adverse events (AEs). Secondary endpoints included major pathological response (MPR), R0 resection rate, interval to surgery, and 30-day complications. This trial was registered at chictr.org.cn, ChiCTR2100045659. RESULTS: From July 2020 to June 2021, 30 patients were enrolled. All patients successfully completed 2 cycles of nICT. AEs were common during nICT, and the most common AE was anorexia (20/30, 67%). However, only one patient with grade 3 ESCC had increased transaminase. According to radiologic evaluations, the objective response rate (ORR) was 67% (20/30) and the disease control rate 97% (29/30). Twenty-three patients underwent McKeown minimally invasive esophagectomy (MIE). The pCR rate of the primary tumor was 21.7%, and the MPR rate of the primary tumor was 52.2%. The median interval to surgery was 40 days, and no patients delayed surgery due to AEs. Pneumonia was the most common major 30-day postoperative complication (9/23, 39%). Anastomotic leakage (AL) occurred in two patients during the hospital stay, and one patient was readmitted due to AL. There was no treatment- or surgery-related deaths. CONCLUSIONS: Neoadjuvant sintilimab plus chemotherapy for locally advanced ESCC appears to be safe and feasible with limited AEs, high R0 resection rate, promising pCR rate, and manageable postoperative complications. Long-term follow-up is required. A multicenter, randomized, phase III clinical trial assessing the efficacy and safety of sintilimab versus placebo in combination with chemotherapy in locally advanced ESCC is warranted to confirm these results. CI - 2021 Annals of Translational Medicine. All rights reserved. FAU - Zhang, Zhenyang AU - Zhang Z AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China. FAU - Hong, Zhi-Nuan AU - Hong ZN AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Fujian Medical University, Fuzhou, China. FAU - Xie, Shuhan AU - Xie S AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Fujian Medical University, Fuzhou, China. FAU - Lin, Wenwei AU - Lin W AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. FAU - Lin, Yukang AU - Lin Y AD - Fujian Medical University, Fuzhou, China. FAU - Zhu, Jiafu AU - Zhu J AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. FAU - Yang, Xiaojie AU - Yang X AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. FAU - Lin, Zhiwei AU - Lin Z AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. FAU - Lin, Jiangbo AU - Lin J AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China. FAU - Kang, Mingqiang AU - Kang M AD - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC8640906 OTO - NOTNLM OT - Esophageal squamous cell carcinoma (ESCC) OT - clinical trial OT - neoadjuvant immunochemotherapy (nICT) OT - phase II COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-5381). The authors have no conflicts of interest to declare. EDAT- 2021/12/21 06:00 MHDA- 2021/12/21 06:01 PMCR- 2021/11/01 CRDT- 2021/12/20 06:19 PHST- 2021/09/16 00:00 [received] PHST- 2021/10/29 00:00 [accepted] PHST- 2021/12/20 06:19 [entrez] PHST- 2021/12/21 06:00 [pubmed] PHST- 2021/12/21 06:01 [medline] PHST- 2021/11/01 00:00 [pmc-release] AID - atm-09-21-1623 [pii] AID - 10.21037/atm-21-5381 [doi] PST - ppublish SO - Ann Transl Med. 2021 Nov;9(21):1623. doi: 10.21037/atm-21-5381.