Details

Autor(en) / Beteiligte

• Mai, Hai-Qiang
• Chen, Qiu-Yan
• Chen, Dongping
• Hu, Chaosu
• Yang, Kunyu
• Wen, Jiyu
• Li, Jingao
• Shi, Ying-Rui
• Jin, Feng
• Xu, Ruilian
• Pan, Jianji
• Qu, Shenhong
• Li, Ping
• Hu, Chunhong
• Liu, Yi-Chun
• Jiang, Yi
• He, Xia
• Wang, Hung-Ming
• Lim, Wan-Teck
• Liao, Wangjun
• He, Xiaohui
• Chen, Xiaozhong
• Liu, Zhigang
• Yuan, Xianglin
• Li, Qi
• Lin, Xiaoyan
• Jing, Shanghua
• Chen, Yanju
• Lu, Yin
• Hsieh, Ching-Yun
• Yang, Muh-Hwa
• Yen, Chia-Jui
• Samol, Jens
• Feng, Hui
• Yao, Sheng
• Keegan, Patricia
• Xu, Rui-Hua

Titel

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

Ist Teil von

• Nature medicine, 2021-09, Vol.27 (9), p.1536-1543

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (irAEs) (39.7 versus 18.9%) and grade ≥3 irAEs (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. Interim analysis from the randomized phase 3 JUPITER-02 trial shows that the addition of anti-PD-1 toripalimab to standard gemcitabine/cisplatin as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma has manageable toxicity and improves progression-free survival, suggesting a potential new treatment standard in this setting.