Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Summary

Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal cancer (EC). However, only 20% to 40% of EC patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with favorable prognosis. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. The aim of this study was to evaluate the efficacy and safety of the combination of toripalimab (an anti-PD-1 antibody) combined with neoadjuvant CRT in locally advanced esophageal squamous cell carcinoma (ESCC).

Timeline

Start

2019-06-25

Primary completion

2020-06-30

Completion

2020-12-31

Outcome

Missed primary endpoint

paper Compared with the control cohort, the pCR rate of the study group was higher but without significant difference (50% vs. 36%, P = 0.19). PMID 37560259 ↗

paper Toripalimab combined with NCRT failed to show significantly better pCR rate than historical data. PMID 37560259 ↗

Publications

• Background Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.
• Results Fu J, Wang F, Dong LH, Zhang J, Deng CL, Wang XL, Xie XY, Zhang J, Deng RX, Zhang LB, Wu H, Feng H, Chen B, Song HF. Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody. Acta Pharmacol Sin. 2017 May;38(5):710-718. doi: 10.1038/aps.2016.161. Epub 2017 Mar 20.
• Results Tang B, Yan X, Sheng X, Si L, Cui C, Kong Y, Mao L, Lian B, Bai X, Wang X, Li S, Zhou L, Yu J, Dai J, Wang K, Hu J, Dong L, Song H, Wu H, Feng H, Yao S, Chi Z, Guo J. Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients. J Hematol Oncol. 2019 Jan 14;12(1):7. doi: 10.1186/s13045-018-0693-2.
• Mai Z, Kongjia L, Wang X, Xie X, Pang L, Yang H, Wen J, Fu J. Impaired TGF-beta signaling via AHNAK family mutations elicits an esophageal cancer subtype with sensitivities to genotoxic therapy and immunotherapy. Cancer Immunol Immunother. 2024 Sep 5;73(11):225. doi: 10.1007/s00262-024-03798-z.
• Chen R, Liu Q, Li Q, Zhu Y, Zhao L, Liu S, Chen B, Liu M, Hu Y, Lin T, Li J, Chen J, Lv Y, Fu J, Xi M, Yang H. A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901). EClinicalMedicine. 2023 Jul 26;62:102118. doi: 10.1016/j.eclinm.2023.102118. eCollection 2023 Aug.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Toripalimab	Monoclonal antibody	240 mg	Intravenous
Background	Cisplatin	Other / unclassified	25 mg/m2	—
Background	Paclitaxel	Small molecule	50 mg/m2	—

Indications