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Third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer

Robert Pirker1

  • 1Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Current Opinion in Oncology
|January 1, 2016
PubMed
Abstract

Insights

Third-generation tyrosine kinase inhibitors (TKIs) show promise for treating non-small cell lung cancer (NSCLC) with EGFR mutations. These novel TKIs are effective against resistance mutations like T790M, offering new hope for patients.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Non-small cell lung cancer (NSCLC) with EGFR mutations often develops resistance to standard tyrosine kinase inhibitor (TKI) therapies.
  • The T790M mutation is a key mechanism of acquired resistance in approximately half of these patients.
  • Developing novel therapeutic strategies is crucial for overcoming TKI resistance in EGFR-mutated NSCLC.

Purpose of the Study:

  • To review the clinical development and efficacy of third-generation EGFR TKIs.
  • To highlight the potential of these novel agents in overcoming TKI resistance.
  • To provide an overview of the current therapeutic landscape for advanced EGFR mutation-positive NSCLC.

Main Methods:

  • Review of clinical trial data for third-generation EGFR TKIs.
  • Analysis of efficacy and safety profiles from phase I/II and phase III trials.
  • Focus on agents targeting EGFR-activating mutations and the T790M resistance mutation.

Main Results:

  • Third-generation TKIs, including osimertinib and rociletinib, have demonstrated clinical activity in patients with acquired resistance to earlier-generation TKIs.
  • Osimertinib and rociletinib are advancing through phase III trials for first- and second-line treatment of advanced EGFR-positive NSCLC.
  • HM61713 is an additional third-generation TKI in early stages of clinical development.

Conclusions:

  • Third-generation EGFR TKIs exhibit significant activity in patients who have developed resistance to first- and second-generation TKIs.
  • These novel agents hold promise for improving clinical outcomes in patients with advanced EGFR mutation-positive NSCLC.
  • The ongoing clinical evaluation of third-generation TKIs represents a significant advancement in NSCLC treatment.

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