Erlotinib in African Americans With Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study With Genetic and Pharmacokinetic Analyses

• Published in: Clinical pharmacology and therapeutics 2014-08, Vol.96 (2), p.182-191
• Main Authors: Phelps, M A, Stinchcombe, T E, Blachly, J S, Zhao, W, Schaaf, L J, Starrett, S L, Wei, L, Poi, M, Wang, D, Papp, A, Aimiuwu, J, Gao, Y, Li, J, Otterson, G A, Hicks, W J, Socinski, M A, Villalona-Calero, M A
• Format: Article
• Language: English
• Subjects: Adult; African Americans - genetics; Aged; Aged, 80 and over; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Erlotinib Hydrochloride; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Pharmacogenetics; Pharmacology. Drug treatments; Pneumology; Prospective Studies; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - therapeutic use; Quinazolines - pharmacokinetics; Quinazolines - therapeutic use; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1038/clpt.2014.93

Prospective studies on epidermal growth factor receptor (EGFR) inhibitors in African Americans with non–small cell lung cancer (NSCLC) have not previously been performed. In this phase II randomized study, 55 African Americans with NSCLC received 150 mg/day erlotinib or a body weight–adjusted dose with subsequent escalations to the maximum‐allowable dose, 200 mg/day, to achieve rash. Erlotinib and OSI‐420 exposures were lower than those observed in previous studies, consistent with CYP3A pharmacogenetics implying higher metabolic activity. Tumor genetics showed only two EGFR mutations, EGFR amplification in 17/47 samples, eight KRAS mutations, and five EML4‐ALK translocations. Although absence of rash was associated with shorter time to progression (TTP), disease‐control rate, TTP, and 1‐year survival were not different between the two dose groups, indicating the dose‐to‐rash strategy failed to increase clinical benefit. Low incidence of toxicity and low erlotinib exposure suggest standardized and maximum‐allowable dosing may be suboptimal in African Americans. Clinical Pharmacology & Therapeutics (2014); 96 2, 182–191. doi:10.1038/clpt.2014.93