The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis.
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.
Biotherapy Center, Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
Tengfei
T
Zhang
School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China.
Jing
J
Xie
Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.|Department of Urology, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Japan.
Seiji
S
Arai
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Liping
L
Wang
Department of Epidemiology and Biostatistics, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Xuezhong
X
Shi
Comprehensive Cancer Center, the Ohio State University, Columbus, Ohio, United States.
Ni
N
Shi
Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
Fen
F
Ma
Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
Sen
S
Chen
Biotherapy Center, Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Lan
L
Huang
Biotherapy Center, Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Li
L
Yang
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Wang
W
Ma
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science (307 Hospital, PLA), Beijing, China.
Bin
B
Zhang
Molecular and Immunological/Bio-therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing China.
Weidong
W
Han
Biotherapy Center, Cancer Center, Sun Yat-sen University, Guangzhou, Guangzhou, Guangdong, China.
Jianchuan
J
Xia
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science (307 Hospital, PLA), Beijing, China.
Hu
H
Chen
Biotherapy Center, Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Henan Key Laboratory for Tumor Immunology and Biotherapy, Henan, China.|School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Yi
Y
Zhang
D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D014408:Biomarkers, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016017:Odds Ratio; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D019233:Retreatment; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab
PD-1; PD-L1; advanced or refractory cancer; immunotherapy; meta-analysis
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