title: Afatinib: An overview of its clinical development in non-small-cell lung cancer and other tumors.
abstract: Afatinib is an oral, irreversible, tyrosine kinase inhibitor (TKI) of EGFR, HER2 and HER4. According to phase I studies, the recommended dose of afatinib was 50mg daily. Rash, acne, diarrhea and stomatitis were the most common adverse events. Afatinib failed to demonstrate an improvement in overall survival in unselected heavily pretreated NSCLC patients (Lux-Lung-1). On the contrary, the Lux-Lung-3 and -6 trials met the primary end point, demonstrating a significant increase in terms of PFS with afatinib compared with chemotherapy in the first line treatment of EGFR mutant patients. Moreover, in both studies, afatinib improved overall survival in patients with exon 19 EGFR deletion (31.7 vs 20.7 months; HR: 0.59, p=0.0001). The results of ongoing randomized trials should further clarify the efficacy of afatinib compared with first-generation TKIs in advanced NSCLC, its activity in the adjuvant and neoadjuvant settings, as well as its efficacy in other tumors.
authors: Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy; Clinical Trials Unit, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli, Italy.
authors: Pasqualina
authors: P
authors: Giordano
authors: Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
authors: Anna
authors: A
authors: Manzo
authors: Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
authors: Agnese
authors: A
authors: Montanino
authors: Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
authors: Raffaele
authors: R
authors: Costanzo
authors: Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
authors: Claudia
authors: C
authors: Sandomenico
authors: Clinical Trials Unit, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli, Italy.
authors: Maria Carmela
authors: MC
authors: Piccirillo
authors: Clinical Trials Unit, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli, Italy.
authors: Gennaro
authors: G
authors: Daniele
authors: Cellular Biology and Biotherapy, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli, Italy; Centro di Ricerche Oncologiche di Mercogliano (CROM), Mercogliano, Avellino, Italy.
authors: Nicola
authors: N
authors: Normanno
authors: Department of Oncology and Hematology, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy.
authors: Guido
authors: G
authors: Carillio
authors: Thoracic Surgery, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli, Italy.
authors: Gaetano
authors: G
authors: Rocco
authors: Department of Clinical Medicine and Surgery, University Federico II, Napoli, Italy.
authors: Roberto
authors: R
authors: Bianco
authors: Clinical Trials Unit, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli, Italy.
authors: Francesco
authors: F
authors: Perrone
authors: Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy. Electronic address: a.morabito@istitutotumori.na.it.
authors: Alessandro
authors: A
authors: Morabito
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D066246:ErbB Receptors
keywords: Afatinib; Clinical trials; EGFR; Head-neck; NSCLC