title: [A new perspective in the treatment of non-small-cell lung cancer (NSCLC). Role of afatinib: An oral and irreversible ErbB family blocker].
abstract: Tyrosine kinase inhibitors (TKI) that block epidermal growth factor receptor (EGFR) pathway have demonstrated a clinical benefit for patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. The currently available TKI (gefitinib and erlotinib) are EGFR reversible inhibitors. Afatinib is an oral, irreversible ErbB family blocker that covalently binds and blocks signaling from EGFR (ErbB1), HER2 (ErbB2) and ErbB4. The compound inhibits also the transphosphorylation of ErbB3. With this mode of action, afatinib is thought to have a mechanistic advantage over EGFR blockade alone, in that it provides a sustained, covalent inhibition of ErbB homo- and hetero-dimers. In the pivotal LUX-Lung 3 study, afatinib demonstrated a prolonged progression free survival over standard pemetrexed plus cisplatin chemotherapy (11.1 versus 6.9 months; HR = 0.58, 95% CI: 0.43-0.78; P = 0.001) in EGFR mutation positive NSCLC patients. The compound has recently been granted a marketing authorization (MA) for the treatment of patients with locally advanced or metastatic NSCLC with activating EGFR mutation(s) and EGFR TKI-naive. In this paper are summarized the efficacy and safety data in this indication.
authors: AP-HP, Hôpital Tenon, Service de pneumologie, 4, rue de la Chine, 75020 Paris, France.
authors: Marie
authors: M
authors: Wislez
authors: Hôpital Gustave-Roussy, Service d'oncologie digestive, 94800 Villejuif, France.
authors: David
authors: D
authors: Malka
authors: Institut de cancérologie de l'Ouest-CRLCC René-Gauducheau, Service d'oncologie médicale, 44805 Nantes Saint-Herblain cedex, France.
authors: Jaafar
authors: J
authors: Bennouna
authors: Centre hospitalier régional universitaire de Lille, Service de dermatologie, 59000 Lille, France.
authors: Laurent
authors: L
authors: Mortier
authors: Centre hospitalier universitaire de Poitiers, Service d'oncologie médicale et de radiologie, 86000 Poitiers, France.
authors: René-Jean
authors: RJ
authors: Bensadoun
authors: Pharmacie d'officine, 51000 Châlons-en-Champagne, France.
authors: Jérôme
authors: J
authors: Sicard
authors: Hôpital Gustave-Roussy, Département des innovations thérapeutiques et des essais précoces, 94800 Villejuif, France.
authors: Pascale
authors: P
authors: Dielenseger
authors: Institut Jean-Godinot, Service de la pharmacie, 51100 Reims, France.
authors: Jean-Baptiste
authors: JB
authors: Rey
authors: Centre hospitalier universitaire de Grenoble, Unité d'oncologie thoracique, 38000 Grenoble, France.
authors: Denis
authors: D
authors: Moro-Sibilot
authors: AP-HP, Hôpital européen Georges-Pompidou, Service d'oncologie médicale et de soins de support, 75015 Paris, France.
authors: Florian
authors: F
authors: Scotté
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D032921:Consensus; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D066247:Receptor, ErbB-4
chemical_list: D000077716:Afatinib; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C508053:ERBB2 protein, human; C587689:ERBB4 protein, human
keywords: EGF-receptor; afatinib; epidermal growth factor (EGF); non-small-cell lung cancer (NSCLC); tyrosine kinase inhibitors (TKI)