Dacomitinib in the Management of Advanced Non-Small-Cell Lung Cancer
The use of targeted therapy in the management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer is an important milestone in the management of advanced lung cancer. There are several generations of EGFR tyrosine kinase inhibitors available for clinical use. Dacomitinib is a second-generation irreversible EGFR tyrosine kinase inhibitor with early-phase clinical studies showing efficacy in non-small-cell lung cancer. In the recently published ARCHER 1050 phase III study, dacomitinib given at 45 mg/day orally was superior to gefitinib, a first-generation reversible EGFR tyrosine kinase inhibitor, in improving both progression-free survival and overall survival when given as first-line therapy. There is no prospective evidence to support the use of dacomitinib as subsequent therapy in patients previously treated with chemotherapy or a first-generation EGFR tyrosine kinase inhibitor such as gefitinib and erlotinib. Dacomitinib has not demonstrated any benefit in unselected patients with non-small-cell lung cancer, and its use should be limited to those with known EGFR-sensitizing mutations. Dacomitinib is associated with increased toxicities of diarrhea, rash, stomatitis, and paronychia compared with first-generation EGFR inhibitors. Global quality of life was maintained when assessed in phase III studies. Overall, dacomitinib is an important first- line agent in EGFR-mutated non-small-cell lung cancer in otherwise fit patients whose toxicities can be well managed.
Editorial support for styling the article as per journal specifications was provided by Brian Szente of InScience Communications, Springer Healthcare (Philadelphia, PA, USA).
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Funding for editorial support for styling the article was provided by Pfizer.
Conflict of interest
Sally C. M. Lau and Ullas Batra have no conflicts of interest that are directly relevant to the content of this article. Tony Mok has received consulting fees/honorarium from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, OncoGenex Pharmaceuticals, Inc., Celgene, Ignyta, Inc., Fishawack Facilitate Ltd, Takeda Oncology, Janssen, Hutchison Chi-Med, OrigiMed, Hengrui Therapeutics Inc., Sanofi-Aventis, R&D, Yuhan Corporation, PrlME Oncology, Amoy Diagnostics Co., Ltd., and Loxo-Oncology. He has also received payment for lectures including speakers’ bureaus from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Novartis, BMS, Taiho, Takeda Oncology, PrlME Oncology, and Amoy Diagnostics Co., Ltd. He has held or currently holds stock/stock options in Sanomics Ltd. and Hutchison Chi-Med. Herbert H. Loong has received research funding from MSD and Mundipharma. He has also served or is currently serving on the advisory boards of Boehringer Ingelheim, Eli Lilly, Novartis, LOXO Pharmaceuticals, and Roche/Genentech. He has received speakers’ fees from AbbVie, Bayer, Eisai Pharmaceuticals, Eli-Lilly, Guardant Health, and Novartis.
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