Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma

Jun Liu; Yang Yang; Zhichao Liu; Xiaolong Fu; Xiaoyue Cai; Hongxuan Li; Li Zhu; Yan Shen; Hong Zhang; Yifeng Sun; Hezhong Chen; Bentong Yu; Renquan Zhang; Jinchen Shao; Ming Zhang; Zhigang Li

doi:10.1136/jitc-2021-004291

Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma

J Immunother Cancer. 2022 Mar;10(3):e004291. doi: 10.1136/jitc-2021-004291.

Authors

Jun Liu¹, Yang Yang², Zhichao Liu², Xiaolong Fu¹, Xiaoyue Cai³, Hongxuan Li¹, Li Zhu⁴, Yan Shen⁴, Hong Zhang², Yifeng Sun², Hezhong Chen⁵, Bentong Yu⁶, Renquan Zhang⁷, Jinchen Shao⁸, Ming Zhang³, Zhigang Li⁹

Affiliations

¹ Department of Radiation Oncology, Shanghai Jiao Tong University, Shanghai, China.
² Department of Thoracic Surgery, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Integrative Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Radiology, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Thoracic Surgery, Changhai Hospital, Shanghai, China.
⁶ Department of Thoracic Surgery, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
⁷ Department of Thoracic Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
⁸ Department of Pathology, Shanghai Jiao Tong University, Shanghai, China.
⁹ Department of Thoracic Surgery, Shanghai Jiao Tong University, Shanghai, China zhigang.li@shsmu.edu.cn.

Abstract

Background: Camrelizumab and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the safety and efficacy of camrelizumab plus neoadjuvant chemotherapy, using pathologically complete response (pCR) as primary endpoint, in the treatment for locally advanced ESCC.

Methods: Patients with locally advanced but resectable thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 1) plus nab-paclitaxel (100 mg/m², day 1, 8, 15) and carboplatin (area under curve of 5 mg/mL/min, day 1) of each 21-days cycle, for two cycles before surgery. The primary endpoint is pCR rate in the per-protocol population. Safety was assessed in the modified intention-to-treat population that was treated with at least one dose of camrelizumab.

Results: From November 20, 2019 to December 22, 2020, 60 patients were enrolled. 55 (91.7%) patients completed the full two-cycle treatment successfully. 51 patients underwent surgery and R0 resection was achieved in 50 (98.0%) patients. pCR (ypT0N0) was identified in 20 (39.2%) patients and 5 (9.8%) patients had complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 58 patients (96.7%) had any-grade treatment-related adverse events (TRAEs), with the most common being leukocytopenia (86.7%). 34 patients (56.7%) had adverse events of grade 3 or worse, and one patient (1.7%) occurred a grade 5 adverse event. There was no in-hospital and postoperative 30-day as well as 90-day mortality.

Conclusions: The robust antitumor activity of camrelizumab and chemotherapy was confirmed and demonstrated without unexpected safety signals. Our findings established camrelizumab and chemotherapy as a promising neoadjuvant treatment for locally advanced ESCC.

Trial registration number: ChiCTR1900026240.

Keywords: Clinical Trials, Phase II as Topic; Combined Modality Therapy; Immunotherapy.

Publication types

Clinical Trial, Phase II
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Esophageal Neoplasms* / pathology
Esophageal Squamous Cell Carcinoma*
Humans
Neoadjuvant Therapy

Substances

Antibodies, Monoclonal, Humanized
camrelizumab