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.
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.
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.
Anti-PD-1/PD-L1 antibodies have high response rates and low adverse effect rates for advanced or refractory cancers.
Oncotarget. 2016 Sep 24 [Epub ahead of print]
Tengfei Zhang, Jing Xie, Seiji Arai, Liping Wang, Xuezhong Shi, Ni Shi, Fen Ma, Sen Chen, Lan Huang, Li Yang, Wang Ma, Bin Zhang, Weidong Han, Jianchuan Xia, Hu Chen, Yi Zhang
Biotherapy Center, Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Center for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia., Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America., Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Department of Epidemiology and Biostatistics, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China., Comprehensive Cancer Center, the Ohio State University, Columbus, Ohio, United States of America., Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science (307 Hospital, PLA), Beijing, China., Molecular and Immunological/Bio-therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing China., Biotherapy Center, Cancer Center, Sun Yat-sen University, Guangzhou, Guangzhou, Guangdong, China.