Afatinib, erlotinib and gefitinib in the first-line therapy of EGFR mutation-positive lung adenocarcinoma: a review.
Non-small cell lung cancer (NSCLC) consists of several histomorphologically defined phenotypes that display an enormous genetic variability. In recent years, epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma has emerged as a unique subset of NSCLC in terms of etiopathogenesis and tumor biology. Since the introduction of the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib, patients with metastatic EGFR mutation-positive lung cancer can be offered a therapeutic alternative that has proven its superiority over standard platinum-based chemotherapy. However, primary or acquired resistance limits the therapeutic success of these targeted agents. Irreversible inhibitors targeting all ErbB family receptor tyrosine kinases, such as afatinib and dacomitinib, have been developed to confer sustained disease control in ErbB-dependent cancers. The large LUX-Lung 3 phase III trial recently reported afatinib to be clearly superior over the most effective platinum doublet in patients with EGFR mutation-positive lung cancer. To fully exploit the clinical activity of afatinib, proactive management of its gastrointestinal and dermatologic toxicities is advised.
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Germany.
Jens
J
Köhler
Martin
M
Schuler
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics*; D000077716:Afatinib; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011799:Quinazolines / Q000008:administration & dosage
D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib