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

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, 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

Abstract

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.

Keywords: PD-1; PD-L1; advanced or refractory cancer; immunotherapy; meta-analysis.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors have declared that no conflicts of interest exits.

Figures

Figure 1. Flow diagram of study selection…
Figure 1. Flow diagram of study selection process
Figure 2. Forest plot for ratio risk…
Figure 2. Forest plot for ratio risk and confidence intervals of response rate (A) and PFS survival (B) of anti-PD-1 antibody compared with other therapies for melanoma
Figure 3. Forest plot for ratio risk…
Figure 3. Forest plot for ratio risk and confidence intervals of adverse effect rate of anti-PD-1 antibody treatment compared with other therapies

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