The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis

• Published in: Oncotarget Vol. 7; no. 45; pp. 73068 - 73079
• Main Authors: Zhang, Tengfei, Xie, Jing, Arai, Seiji, Wang, Liping, Shi, Xuezhong, Shi, Ni, Ma, Fen, Chen, Sen, Huang, Lan, Yang, Li, Ma, Wang, Zhang, Bin, Han, Weidong, Xia, Jianchuan, Chen, Hu, Zhang, Yi
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 08.11.2016
• Subjects: Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; Biomarkers, Tumor; Drug Resistance, Neoplasm; Humans; Immunomodulation - drug effects; Melanoma - drug therapy; Melanoma - pathology; Neoplasm Staging; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Odds Ratio; Prognosis; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Research Paper; Retreatment; Treatment Outcome; PD-L1; meta-analysis; advanced or refractory cancer; PD-1; immunotherapy
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.12230

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.