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Meta-Analysis
. 2013 Jun 13;8(6):e65166.
doi: 10.1371/journal.pone.0065166. Print 2013.

Incidence and risk of treatment-related mortality with mTOR inhibitors everolimus and temsirolimus in cancer patients: a meta-analysis

Wei-Xiang Qi  1 , Yu-Jing Huang, Yang Yao, Zan Shen, Da-Liu Min
Affiliations
Meta-Analysis

Incidence and risk of treatment-related mortality with mTOR inhibitors everolimus and temsirolimus in cancer patients: a meta-analysis

Wei-Xiang Qi et al. PLoS One. .

Abstract

Background: Two novel mammalian targets of rapamycin (mTOR) inhibitors everolimus and temsirolimus are now approved by regulatory agencies and have been widely investigated among various types of solid tumors, but the risk of fatal adverse events (FAEs) with these drugs is not well defined.

Methods: We searched PubMed, EMBASE, and Cochrane library databases for relevant trials. Eligible studies included prospective phase II and III trials evaluating everolimus and temsirolimus in patients with all malignancies and data on FAEs were available. Statistical analyses were conducted to calculate the summary incidence, RRs and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of the included studies.

Results: A total of 3322 patients with various advanced solid tumors from 12 trials were included. The overall incidence of mTOR inhibitors associated FAEs was 1.8% (95%CI: 1.3-2.5%), and the incidences of everolimus related FAEs were comparable to that of temsirolimus (1.7% versus 1.8%). Compared with the controls, the use of mTOR inhibitors was associated with an increased risk of FAEs, with a RR of 3.24 (95%CI: 1.21-8.67, p = 0.019). On subgroup analysis, a non-statistically significant increase in the risk of FAEs was found according to different mTOR inhibitors, tumor types or controlled therapy. No evidence of publication bias was observed.

Conclusion: With the present evidence, the use of mTOR inhibitors seems to increase the risk of FAEs in patients with advanced solid tumors. More high quality trials are still needed to investigate this association.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow chart of trial selection process in the meta-analysis.
Figure 2
Figure 2. Forest plot for meta-analysis of incidence of FAEs in cancer patients assigned mTOR inhibitors.
Figure 3
Figure 3. Relative risk of mTOR inhibitors associated FAEs versus control from randomized controlled trials of patients with cancer.
See this image and copyright information in PMC

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