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First-Line Management of EGFR-Mutated Advanced Lung Adenocarcinoma: Recent Developments

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Abstract

Gefitinib and erlotinib are small-molecule reversible tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR). Objective responses have been observed frequently in patients with non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations, the most common being deletions in exon 19 and the exon 21 L858R mutation. EGFR mutations are prevalent in female patients, those who have never smoked, those of Asian ethnicity and those who have adenocarcinoma histology. Given the efficacy of EGFR TKIs in advanced NSCLC in the salvage setting, and their favourable toxicity profile compared with conventional chemotherapy, there is considerable interest in evaluating their efficacy in the first-line treatment of advanced NSCLC. To date, there have been several phase II and phase III studies that have examined the efficacy of first-line single-agent EGFR TKIs in unselected, clinically selected or molecularly selected populations. Here we review and compare the differences in these phase III trials. Most phase III trials chose progression-free survival (PFS) rather than overall survival (OS) as their primary endpoint. PFS was prolonged but OS was not. The recent development of novel irreversible EGFR TKIs, such as afatinib and dacomitinib, is also reviewed.

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Acknowledgments

No sources of funding were used to assist with the preparation of this review. Dr Yang is an uncompensated advisor for Boehringer Ingelheim and Eli Lilly. He received honoraria for an advisory role or being a speaker from AstraZeneca, Roche, Pfizer, Clovis and Novartis; Dr Lin and Dr Liao have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan

    Bin-Chi Liao

  2. Department of Oncology, National Taiwan University Hospital, 7. Chung-Shan South Road, Taipei, Taiwan

    Bin-Chi Liao, Chia-Chi Lin & James Chih-Hsin Yang

  3. Graduate Institute of Oncology and Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan

    Chia-Chi Lin & James Chih-Hsin Yang

  4. Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Chia-Chi Lin

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  1. Bin-Chi Liao
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Liao, BC., Lin, CC. & Yang, J.CH. First-Line Management of EGFR-Mutated Advanced Lung Adenocarcinoma: Recent Developments. Drugs 73, 357–369 (2013). https://doi.org/10.1007/s40265-013-0020-8

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