Anti-Programmed Cell Death (PD)-1 Immunotherapy for Malignant Tumor: A Systematic Review and Meta-Analysis

Ran Chen, Pei-Chun Peng, Bin Wen, Fu-Ying Li, Sheng Xie, Guozhong Chen, Jiefu Lu, Zhuoyu Peng, Shao-Bo Tang, Yu-Mei Liang, Xin Deng, Ran Chen, Pei-Chun Peng, Bin Wen, Fu-Ying Li, Sheng Xie, Guozhong Chen, Jiefu Lu, Zhuoyu Peng, Shao-Bo Tang, Yu-Mei Liang, Xin Deng

Abstract

This systematic review and meta-analysis evaluated anti-programmed cell death (PD)-1 immunotherapy (nivolumab or pembrolizumab) for overall efficacy, safety, and effective dose relative to standard chemotherapy or other conventional drugs in the treatment of malignant tumors. We searched the following databases, PubMed, Medline, Embase, Cochrane, Wangfang Data, Weipu, and China National Knowledge Infrastructure, and the reference lists of the selected articles for randomized controlled trials (RCTs) of anti-PD-1 therapies in humans. The outcome measures were overall survival, treatment response, and adverse events. Only four randomized controlled trials met our inclusion criteria. Three of these evaluated responses to nivolumab, whereas one tested pembrolizumab. The result of our analysis suggested that nivolumab may improve the overall response rate in treating melanoma relative to chemotherapy and has few associated adverse events. Similarly, in metastatic melanoma patients, nivolumab had a significant advantage over dacarbazine in terms of 1-year survival, progression-free survival, and objective response rate. Regarding dose levels of nivolumab for patients with metastatic renal cell carcinoma, the outcomes in response to 2 and 10 mg/kg were similar, but both had significant advantages over 0.3 mg/kg. In addition, pembrolizumab showed similar outcomes in response to 2- and 10-mg/kg treatment. Anti-PD-1 immunotherapy appears to be safe and effective for patients with melanoma or metastatic renal cell carcinoma. Our meta-analysis is limited, but additional clinical trials are warranted to verify this preliminary evidence of positive outcomes and before anti-PD-1 therapy can be recommended for routine clinical use.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Flowchart representing the systematic identification of studies.
Figure 2
Figure 2
Assessment of risk bias.
Figure 3
Figure 3
Forest plot depicting the overall response rate of nivolumab compared with chemotherapy.
Figure 4
Figure 4
Forest plot depicting the comparison of adverse events associated with nivolumab and chemotherapy.
Figure 5
Figure 5
Forest plot depicting the 1-year OS rates of nivolumab and dacarbazine.
Figure 6
Figure 6
Forest plot depicting the PFS rates associated with nivolumab and dacarbazine.
Figure 7
Figure 7
Forest plot depicting the objective response rates associated with nivolumab and dacarbazine.
Figure 8
Figure 8
Forest plot depicting the comparison of adverse events associated with nivolumab and dacarbazine.
Figure 9
Figure 9
Forest plot depicting the overall response rate with different doses (2 and 10 mg/kg) of pembrolizumab.
Figure 10
Figure 10
Forest plot depicting the PFS rates associated with different doses (2 and 10 mg/kg) of pembrolizumab.
Figure 11
Figure 11
Forest plot depicting 1-year survival rates associated with different doses (2 and 10 mg/kg) of pembrolizumab.
Figure 12
Figure 12
Forest plot depicting overall response rates of different doses (0.3 and 2 mg/kg) of nivolumab.
Figure 13
Figure 13
Forest plot depicting the PFS rates associated with different doses (0.3 and 2 mg/kg) of nivolumab.
Figure 14
Figure 14
Forest plot depicting the OS rates associated with different doses (0.3 and 2 mg/kg) of nivolumab.
Figure 15
Figure 15
Forest plot depicting the overall response rates associated with different doses (0.3 and 10 mg/kg) of nivolumab.
Figure 16
Figure 16
Forest plot depicting PFS rates associated with different doses (0.3 and 10 mg/kg) of nivolumab.
Figure 17
Figure 17
Forest plot depicting the OS rates associated with different doses (0.3 and 10 mg/kg) of nivolumab.
Figure 18
Figure 18
Forest plot depicting the overall response rates associated with different doses (2 and 10 mg/kg) of nivolumab.
Figure 19
Figure 19
Forest plot depicting the OS rates associated with different doses (2 and 10 mg/kg) of nivolumab.
Figure 20
Figure 20
Forest plot depicting the PFS rates associated with different doses (2 and 10 mg/kg) of nivolumab.

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Source: PubMed

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