The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis
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Tengfei Zhang1,2,*, Jing Xie3,*, Seiji Arai2,4, Liping Wang5, Xuezhong Shi6, Ni Shi7, Fen Ma2, Sen Chen2, Lan Huang1, Li Yang1, Wang Ma5, Bin Zhang8, Weidong Han9, Jianchuan Xia10, Hu Chen8, Yi Zhang1,5,11,12
1Biotherapy Center, Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
2Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
3School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China
4Department of Urology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Japan
5Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
6Department of Epidemiology and Biostatistics, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China
7Comprehensive Cancer Center, the Ohio State University, Columbus, Ohio, United States
8Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science (307 Hospital, PLA), Beijing, China
9Molecular and Immunological/Bio-therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing China
10Biotherapy Center, Cancer Center, Sun Yat-sen University, Guangzhou, Guangzhou, Guangdong, China
11Henan Key Laboratory for Tumor Immunology and Biotherapy, Henan, China
12School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
*These authors contributed equally to this work
Yi Zhang, email: [email protected]
Hu Chen, email: [email protected]
Keywords: PD-1, PD-L1, immunotherapy, advanced or refractory cancer, meta-analysis
Received: May 27, 2016 Accepted: September 17, 2016 Published: September 24, 2016
Purpose: To systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer.
Results: Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53−2.41), 21% (95% CI: 17%−25%) and 21% (95% CI: 16%−27%) respectively. While the overall adverse effects rate for melanoma, NSCLC, RCC were 16% (95% CI: 6%−28%), 11% (95% CI: 8%−14%) and 20% (95% CI: 11%−32%) respectively. Tumor PD-L1 expression and patient smoking status might serve as biomarkers to predict response of anti-PD-1/PD-L1 antibody treatment. Compared to tumors with negative PD-L1 expression, tumors with positive PD-L1 expression had a significantly higher clinical response rate (41.4% versus 26.5%) with RR = 1.92 (95% CI: 1.53−2.41, P < 0.001). Smoker patients also showed a significantly higher response rate (33.7%) than patients who never smoked (4.2%) with RR = 6.02 (95% CI: 1.22−29.75, P = 0.028). Nivolumab and Pembrolizumab were associated with significantly increased response rate (RR = 2.89, 95% CI: 2.46−3.40, P < 0.001), reduced death risk (HR= 0.53; 95% CI: 0.48−0.57; P < 0.001), and decreased adverse effect rate (RR = 0.49, 95% CI: 0.30−0.80, P = 0.004) compared with other therapies.
Experimental Design: Clinical trials reporting response or safety of anti-PD-1/PD-L1 antibodies for advanced or refractory cancer patients published before January 31th 2016 were searched in PubMed and EMBASE database. Meta-analyses using random effects models were used to calculate the overall estimate.
Conclusions: Anti-PD-1/PD-L1 antibodies have high response rates and low adverse effect rates for advanced or refractory cancers.
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