Overcoming Resistance to EGFR Inhibitors in NSCLC

Author(s): Paolo Maione, Paola C. Sacco, Francesca Casaluce, Assunta Sgambato, Giuseppe Santabarbara, Antonio Rossi, Cesare Gridelli.

Journal Name: Reviews on Recent Clinical Trials

Volume 11 , Issue 2 , 2016

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Abstract:

Background: The clarification of several molecular pathways underlying the tumorigenesis has led to the development of several targeted drugs that have substantially improved the treatment of Non-Small-Cell Lung Cancer (NSCLC). The Epidermal Growth Factor Receptor (EGFR) is the target of several Tyrosine-Kinase Inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. EGFR-TKIs markedly improve progression-free survival of patients with advanced NSCLC with EGFR mutations compared with chemotherapy.

Methods: We undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question.

Results: Although first- and second-generation agents offer in target population (with EGFR mutations) a substantial improvement of outcomes compared with standard chemotherapy, unfortunately, drug resistance develops after initial benefit, through a variety of mechanisms. Novel- (third) generation EGFR inhibitors have a selective mechanism of action and are currently in advanced clinical development, producing encouraging results in patients with acquired resistance to previous generation agents.

Conclusion: The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC, and third-generation EGFR inhibitors are the most promising approach to the issue.

Keywords: AZD9291, EGFR mutations, rociletinib, selective EGFR inhibitors, T790M.

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Article Details

VOLUME: 11
ISSUE: 2
Year: 2016
Page: [99 - 105]
Pages: 7
DOI: 10.2174/1574887111666160330120431

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