Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial

• Published in: Nature medicine Vol. 30; no. 1; pp. 249 - 256
• Main Authors: Jiang, Zefei, Ouyang, Quchang, Sun, Tao, Zhang, Qingyuan, Teng, Yuee, Cui, Jiuwei, Wang, Haibo, Yin, Yongmei, Wang, Xiaojia, Zhou, Xin, Wang, Yongsheng, Sun, Gang, Wang, Jingfen, Zhang, Lili, Yang, Jin, Qian, Jun, Yan, Min, Liu, Xinlan, Yi, Tienan, Cheng, Ying, Li, Man, Zang, Aimin, Wang, Shusen, Wang, Chuan, Wu, Xinhong, Cheng, Jing, Li, Hui, Lin, Ying, Geng, Cuizhi, Gu, Kangsheng, Xie, Chunwei, Xiong, Huihua, Wu, Xiaohong, Yang, Junlan, Li, Qingshan, Chen, Yiding, Li, Fanfan, Zhang, Anqin, Zhang, Yongqiang, Wu, Yudong, Nie, Jianyun, Liu, Qiang, Wang, Kun, Mo, Xueli, Chen, Lilin, Pan, Yueyin, Fu, Peifen, Zhang, Helong, Pang, Danmei, Sheng, Yuan, Han, Yunwei, Wang, Hongxia, Cang, Shundong, Luo, Xianming, Yu, Wenbo, Deng, Rong, Yang, Chaoqiang, Keegan, Patricia
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 2024; Nature Publishing Group
• Subjects: 692/308/2779/777; 692/699/67/1347; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Chemotherapy; Confidence intervals; Immune checkpoint inhibitors; Infectious Diseases; Metabolic Diseases; Metastases; Metastasis; Molecular Medicine; Neurosciences; Paclitaxel; PD-L1 protein; Placebos; Safety; Statistical analysis; Survival
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-023-02677-x

The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) ( n  = 353; experimental arm) versus placebo and nab-P ( n  = 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470–0.906, P  = 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414–0.914, P  = 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579 . In this prespecified analysis of the ongoing TORCHLIGHT phase 3 trial, first-line treatment with toripalimab and nab-paclitaxel in patients with advanced triple-negative breast cancer led to significantly longer progression-free survival in the PD-L1-positive population compared to nab-paclitaxel alone.