Neoadjuvant sintilimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, single-center, phase 2 trial (ESONICT-1)

Zhenyang Zhang; Zhi-Nuan Hong; Shuhan Xie; Wenwei Lin; Yukang Lin; Jiafu Zhu; Xiaojie Yang; Zhiwei Lin; Jiangbo Lin; Mingqiang Kang

doi:10.21037/atm-21-5381

Neoadjuvant sintilimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, single-center, phase 2 trial (ESONICT-1)

Ann Transl Med. 2021 Nov;9(21):1623. doi: 10.21037/atm-21-5381.

Authors

Zhenyang Zhang^#^{1

2}, Zhi-Nuan Hong^#^{1

3}, Shuhan Xie^#^{1

3}, Wenwei Lin¹, Yukang Lin³, Jiafu Zhu¹, Xiaojie Yang¹, Zhiwei Lin¹, Jiangbo Lin^#^{1

2}, Mingqiang Kang^#^{1

2}

Affiliations

¹ Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
² Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China.
³ Fujian Medical University, Fuzhou, China.

^# Contributed equally.

Abstract

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/m²) on day 1, albumin-bound paclitaxel (125 mg/m²) 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.

Keywords: Esophageal squamous cell carcinoma (ESCC); clinical trial; neoadjuvant immunochemotherapy (nICT); phase II.