title: The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer.
abstract: Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) represents a distinct disease entity whose molecular phenotype predicts exquisite sensitivity to the reversible EGFR-tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib. However, primary or acquired resistance to these agents remains a major clinical problem. Afatinib is a novel dual irreversible EGFR/HER2 TKI that has been shown in preclinical studies to potentially prevent, delay or overcome resistance to reversible EGFR-TKIs. On this basis, the LUX-Lung clinical trial program has been recently launched for testing this molecule in advanced NSCLC patients. Notably, early results from the randomized LUX-Lung 1 trial indicate that afatinib significantly prolongs progression-free survival compared with placebo in pretreated patients with clinically acquired resistance to gefitinib or erlotinib. On the other hand, the LUX-Lung 2 trial shows that afatinib is highly active in the EGFR-mutant subgroup of patients. While these preliminary data open a new exciting scenario for the future development of anti-EGFR therapies in NSCLC, ongoing afatinib trials will definitively establish a role for this molecule in the treatment of advanced NSCLC.
authors.affiliation: Division of Medical Oncology, Azienda Ospedaliera S Maria della Misericordia, via Dottori, 1, Perugia 06156, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib