Influence of SNVs on adverse reactions and survival in gefitinib-treated lung cancer patients from a preliminary study

Gefitinib is indicated for metastatic non-small cell lung cancer (NSCLC) with active mutations in the epidermal growth factor receptor (EGFR) gene; however, its use is frequently associated with dermatological, gastrointestinal, and hepatic adverse drug reactions (ADRs). This study investigated whether single-nucleotide variants (SNVs) in the EGFR, ABCB1, and ABCG2 influence gefitinib-related ADRs and survival in patients with NSCLC. This retrospective cohort study included patients with NSCLC harboring EGFR mutations in exons 19, 20, or 21, who were treated with gefitinib (250 mg/day). Genotyping was performed using real-time PCR, and ADRs were classified according to the Common Terminology Criteria for Adverse Events, version 5. The ABCB1 rs2032582 non-CC genotype was associated with a higher risk of diarrhea (p = 0.0344, OR = 7.579) than the CC genotype. The AA genotype was associated with a higher risk of death (p = 0.0048; HR = 32.498) than the CA, CCCC/CA/CT, and TT genotypes. Our findings suggest that ABCB1 SNVs influence gefitinib-related ADRs and patient survival in NSCLC. However, as this was an exploratory and preliminary study, further investigations with larger and more robust cohorts are essential to confirm and validate these findings.