title: Epidermal Growth Factor Receptor Mutated Advanced Non-Small Cell Lung Cancer: A Changing Treatment Paradigm.
abstract: Activating mutations in the epidermal growth factor receptor (EGFR) are present in approximately 15% of US patients with lung adenocarcinoma. EGFR tyrosine kinase inhibitors are associated with high response rate and progression-free survival for patients with non-small cell lung cancer with this genotype. Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved. This article reviews the current treatments, resistance mechanisms, and strategies to overcome resistance.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Clifton Rd, Atlanta, GA 30322, USA. Electronic address: Suchita.pakkala@emoryhealthcare.org.
authors.forename: Suchita
authors.initials: S
authors.lastname: Pakkala
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Clifton Rd, Atlanta, GA 30322, USA.
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
mesh_terms: D000178:Acrylamides; D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D000077716:Afatinib; D019943:Amino Acid Substitution; D000814:Aniline Compounds; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D020125:Mutation, Missense; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D007211:Indoles; D011743:Pyrimidines
chemical_list: D000178:Acrylamides; D000077716:Afatinib; D000814:Aniline Compounds; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines; C512478:EGFR protein, human
keywords: Afatinib; Epidermal growth factor receptor (EGFR); Erlotinib; Gefitinib; Non–small cell lung cancer; Osimertinib; TKI resistance; Tyrosine kinase inhibitors (TKI)