1237PASSOCIATION OF PHARMACOKINETICS OR PHARMACOGENOMICS WITH TOXICITY OF ERLOTINIB IN PATIENTS WITH RECURRENT ADVANCED NON-SMALL CELL LUNG CANCER

ABSTRACT Aim: Erlotinib is a potent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and is a key drug for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutation. The orally administered erlotinib showed large interindividual variability in its pharmacokinetics. The aim of this study was to evaluate the association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced NSCLC. Methods: The evaluation of pharmacokinetics was performed using samples obtained on day 1 at 0, 1, 2, 4, 6, 8, 24 hour and day 8 and day 15 after starting of erlotinib 150 mg administration. Plasma concentrations of erlotinib were analyzed by high-performance liquid chromatography. The genotypes of ABCG2, ABCB1, ABCC2, CYP3A4, CYP3A5, CYP1A1, and CYP1A2 were analyzed by direct sequencing. Results: From January 2010 through June 2012, 25 patients with advanced NSCLC (18 men and 7 women; median age, 68 years; range, 31 to 80 years) were enrolled. 17 patients had adenocarcinoma, 8 had squamous cell carcinoma, and 1 was other. Four patients were EGFR mutation positive, 14 were negative, and 8 were unknown. There were no statistically significant associations of pharmacokinetics or pharmacogenomics with toxicity, such as skin toxicity, diarrehea, stomatitis, liver injury, and interstitial lung disease (ILD) of erlotinib. However, one patient who died of drug induced ILD was homozygous for ABCG2 C > A and showed the highest AUC. Additionally, Cmax was trending towards a higher value in 4 patients with liver injury than in those without (p = 0.054). Conclusions: The homozygote of ABCG2 C > A could be associated with elevated erlotinib exposure and drug induced ILD. Further studies of the association of pharmacokinetics or pharmacogenomics with toxicity of EGFR tyrosine kinase inhibitor are needed. Disclosure: All authors have declared no conflicts of interest.