Afatinib: An overview of its clinical development in non-small-cell lung cancer and other tumors

Critical Reviews in Oncology/hematology
Pasqualina GiordanoAlessandro Morabito

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.

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Citations

Mar 16, 2018·Drugs & Therapy Perspectives : for Rational Drug Selection and Use·Emma D Deeks, Gillian M Keating
Feb 1, 2018·Therapeutic Advances in Medical Oncology·Malgorzata MilewskaAlex J Eustace
Apr 1, 2020·Chemical Society Reviews·Ayah AbdeldayemPatrick T Gunning
Nov 23, 2016·Targeted Oncology·Gillian M Keating
Aug 21, 2020·European Journal of Medicinal Chemistry·Yuemin BianXiang-Qun Xie
Aug 28, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yuan LiangJie Zhang

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