Afatinib: a second-generation EGF receptor and ErbB tyrosine kinase inhibitor for the treatment of advanced non-small-cell lung cancer

• Published in: Future oncology (London, England) Vol. 11; no. 18; pp. 2525 - 2540
• Main Authors: Marquez-Medina, Diego, Popat, Sanjay
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01-09-2015
• Subjects: adenocarcinoma; Afatinib; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Clinical Trials as Topic; Dosage and administration; Drug therapy; EGF receptor; Epidermal growth factor; ErbB Receptors - antagonists & inhibitors; ErbB2; ErbB4; Humans; irreversible; Kinases; Ligands; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Mutation; Neoplasm Staging; Non-small cell lung cancer; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Quality of life; Quinazolines - pharmacology; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; second generation; squamous; Treatment Outcome; tyrosine kinase inhibitor; afatinib; squamous; ErbB2; second generation; ErbB4; irreversible; EGF receptor; adenocarcinoma; tyrosine kinase inhibitor; non-small-cell lung cancer
• ISSN: 1479-6694; 1744-8301
• DOI: 10.2217/fon.15.183

First-generation reversible EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) changed our understanding of advanced non-small-cell lung cancer biology and behavior. The presence of sensitizing
mutations in advanced non-small-cell lung cancer defines a subset of patients with a better prognosis and sensitivity to EGFR-TKIs with a better response rate, progression-free survival, quality of life and symptom control than with chemotherapy in the first-line therapy setting. However, current EGFR-TKIs show minimal responses in
wild-type patients or with acquired TKI resistance mediated through the
T790M allele. Afatinib is an irreversible pan-ErbB-TKI, active against wild-type
, sensitizing and T970M-mutant
, ErbB2 and ErbB4 receptors, and represents a step change between reversible first-generation and future irreversible highly specific third-generation EGFR-TKIs. Here, we review the clinical development of afatinib through the LUX-Lung trials portfolio highlighting benefits and toxicities.