Abstract
Patients with advanced non-small-cell lung cancer who are treated with pemetrexed display a wide variation in clinical response and toxicity. In this prospective, multicentre cohort study, we investigated the association with treatment effectiveness and toxicity of 10 polymorphisms in nine candidate genes, covering the folate pathway (MTHFR), cell transport (SLC19A1/ABCC2/ABCC4), intracellular metabolism (FPGS/GGH) and target enzymes (TYMS/DHFR/ATIC) of pemetrexed. Adjusted for sex, ECOG performance score and disease stage, the association between ATIC (rs12995526) and overall survival (HR 1.59, 95% CI 1.06 to 2.39) was significant. Regarding toxicity, this ATIC polymorphism was significantly associated with severe laboratory (p=0.014) and clinical (p=0.016) chemotherapy-related adverse events, severe neutropenia (p=0.007) and all-grade diarrhoea (p=0.034) in multivariable analyses.
| Original language | English |
|---|---|
| Pages (from-to) | 1150-1153 |
| Number of pages | 4 |
| Journal | Thorax |
| Volume | 76 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 1 Nov 2021 |
Bibliographical note
Funding Information:Funding This work was supported by ZonMw, the Netherlands (grant number 152001017, Biomarkers for improving the cost-effectiveness and safety of pemetrexed). For a part of the research, funding was received from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 116 030. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Publisher Copyright:
© Author(s) (or their employer(s)) 2021.
