Systematic review and meta-analysis of the predictive power of MTHFR polymorphisms for pemetrexed drug efficacy and toxicity in non-small cell lung cancer patients

Abstract

We conducted a meta-analysis to determine if MTHFR polymorphisms are effective biomarkers for non-small cell lung cancer (NSCLC) patient survival and pemetrexed (PEM) treatment toxicity. Because of data heterogeneity, fixed or random effects models were chosen, and pooled HRs and 95% confidence intervals (CIs) were calculated. No correlation between MTHFR 677 C > T polymorphism and progression-free survival (PFS) or overall survival (OS) was detected in NSCLC patients; however, patients with the T allele benefited more than those with the wild-type allele. Two papers reported hematologic toxicity of single-agent PEM treatment in patients with the MTHFR 677 C > T polymorphism. However, data on MTHFR polymorphisms and toxicity could not be combined, even though publication bias and sensitivity analysis results were stable and reliable. We conclude that the MTHFR 677 C > T polymorphism could not predict PEM efficacy in NSCLC patients; however, the T allele may increase the risk of haematological toxicity. A large-scale clinical trial is recommended.

Keywords:

• pemetrexed (PEM)
• pharmacogenomics
• survival
• adverse drug reaction

Acknowledgments

We would like to thank Editage (http://www.editage.com) for English language editing and publication support.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Science Foundation of Peking University Cancer Hospital 2020-27.