Increased risk of severe infections in non-small-cell lung cancer patients treated with pemetrexed: a meta-analysis of randomized controlled trials

Abstract

Background and aims: Infections related to pemetrexed have been reported in clinical trials. It is not yet clear whether this drug increases infection risk or not. This meta-analysis assessed the overall incidence and risk of severe infections (≥ grade 3) associated with the use of pemetrexed in non-small-cell lung cancer patients.

Methods: The databases of PubMed, Embase, and the Cochrane Library were searched for relevant studies published up to December 2015. Eligible studies included randomized controlled trials (RCTs) of pemetrexed for non-small-cell lung cancer patients that reported grade 3–5 infection and febrile neutropenia. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models, according to the heterogeneity of the included studies.

Results: Seven randomized controlled trials were included, comprising 1848 patients. The incidence of severe infection and febrile neutropenia due to pemetrexed was 5.7% (95% CI: 3.2–8.3%) and 1.3% (95% CI: 0.7–2.0%), respectively. The use of pemetrexed was associated with an increased risk of severe infection (RR 1.61, 95% CI: 1.07–2.44, P = .02) and febrile neutropenia (RR 4.28, 95% CI: 1.08–17.01, P = .04).

Conclusion: The use of pemetrexed was associated with an increased risk of developing severe infections and febrile neutropenia in non-small-cell lung cancer patients. Frequent clinical monitoring and management of infections should be emphasized during pemetrexed treatment. More studies are needed to reveal the mechanism of the increased risk of severe infections.

Keywords:

• Adverse events
• Cancer
• Infections
• Meta-analysis
• Pemetrexed

Transparency

Declaration of funding

This study was supported by a grant from the National Natural Science Foundation of China (81401323).

Declaration of financial/other relationships

T.S., F.K., J.K., Z.W., F.B., W.S.-H., and W.J.-J. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewer 1 has disclosed that he was a regional consultant to Eli Lilly in 2015. Peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgement

We thank Zuo Pei-Yuan for discussions and reading of the manuscript.