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Meta-Analysis
. 2016 Nov 8;7(45):73068-73079.
doi: 10.18632/oncotarget.12230.

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

Tengfei Zhang  1   2 , Jing Xie  3 , Seiji Arai  2   4 , Liping Wang  5 , Xuezhong Shi  6 , Ni Shi  7 , Fen Ma  2 , Sen Chen  2 , Lan Huang  1 , Li Yang  1 , Wang Ma  5 , Bin Zhang  8 , Weidong Han  9 , Jianchuan Xia  10 , Hu Chen  8 , Yi Zhang  1   5   11   12
Affiliations
Meta-Analysis

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

Tengfei Zhang et al. Oncotarget. .

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.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors have declared that no conflicts of interest exits.

Figures

Figure 1
Figure 1. Flow diagram of study selection process
Figure 2
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
Figure 3. Forest plot for ratio risk and confidence intervals of adverse effect rate of anti-PD-1 antibody treatment compared with other therapies
See this image and copyright information in PMC

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