Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial.

Abstract

Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase 3 trial (ClinicalTrials.gov identifier: NCT03581786), 289 patients with RM-NPC and no previous chemotherapy for recurrent or metastatic disease were randomized (1/1) to receive either toripalimab, a monoclonal antibody against human programmed death-1 (PD-1), or placebo in combination with GP every 3 weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee according to RECIST v.1.1. At the prespecified interim PFS analysis, a significant improvement in PFS was detected in the toripalimab arm compared to the placebo arm: median PFS of 11.7 versus 8.0 months, hazard ratio (HR) = 0.52 (95% confidence interval (CI): 0.36-0.74), P = 0.0003. An improvement in PFS was observed across key subgroups, including PD-L1 expression. As of 18 February 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.603 (95% CI: 0.364-0.997)). The incidence of grade ≥3 adverse events (AEs) (89.0 versus 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5 versus 4.9%) and fatal AEs (2.7 versus 2.8%) was similar between the two arms; however, immune-related AEs (39.7 versus 18.9%) and grade ≥3 infusion reactions (7.5 versus 0.7%) were more frequent in the toripalimab arm. In conclusion, the addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS compared to GP alone, and with a manageable safety profile.

• Authors: Hai-Qiang Mai, Qiu-Yan Chen, Dongping Chen, Chaosu Hu, Kunyu Yang, Jiyu Wen, Jingao Li, Ying-Rui Shi, Feng Jin, Ruilian Xu, Jianji Pan, Shenhong Qu, Ping Li, Chunhong Hu, Yi-Chun Liu, Yi Jiang, Xia He, Hung-Ming Wang, Wan-Teck Lim, Wangjun Liao, Xiaohui He, Xiaozhong Chen, Zhigang Liu, Xianglin Yuan, Qi Li, Xiaoyan Lin, Shanghua Jing, Yanju Chen, Yin Lu, Ching-Yun Hsieh, Muh-Hwa Yang, Chia-Jui Yen, Jens Samol, Hui Feng, Sheng Yao, Patricia Keegan, Rui-Hua Xu
• Journal: Nature medicine (Nat Med) Vol. 27 Issue 9 Pg. 1536-1543 (09 2021) ISSN: 1546-170X [Electronic] United States
• PMID: 34341578 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• CD274 protein, human
• Deoxycytidine
• toripalimab
• Cisplatin
• Gemcitabine

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Agents, Immunological (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• B7-H1 Antigen (antagonists & inhibitors, genetics)
• Cisplatin (administration & dosage, adverse effects)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Female
• Humans
• Male
• Middle Aged
• Nasopharyngeal Carcinoma (drug therapy, immunology, pathology)
• Neoplasm Recurrence, Local (drug therapy, immunology, pathology)
• Progression-Free Survival
• Gemcitabine