Should epidermal growth factor receptor tyrosine kinase inhibitors be considered ideal drugs for the treatment of selected advanced non-small cell lung cancer patients?

Antonio Rossi, Raffaella Pasquale, Claudia Esposito, Nicola Normanno

Research output: Contribution to journalArticle

Abstract

An ideal target-based agent for the treatment of cancer patients should fulfil a number of requirements, including the availability of biomarkers to select the target population, superiority over existing treatments and specific advantages in terms of pharmacokinetics and/or metabolism. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib and afatinib, have been investigated in the treatment of non-small cell lung cancer (NSCLC), and to date a large amount of clinical data are available. The activity of EGFR-TKIs was initially investigated in unselected patients leading to unsatisfactory results. However, the discovery that response to EGFR-TKIs is associated with the presence of activating EGFR mutations in NSCLC, has led to the design of clinical trials in which patients were selected on the basis of the EGFR mutational status or of clinical and pathological features that are highly associated with the presence of EGFR mutations. In this respect, several phase III randomized trials have demonstrated that first-line EGFR-TKIs, compared to chemotherapy, is associated with longer progression-free survival, higher response rate, better toxicity profile and quality of life in patients carrying EGFR mutations. Although no survival advantage was demonstrated, all the trials suffered of a high post-progression treatment cross-over, which predictably undermined the results. This review will summarize the current evidence that strongly support the hypothesis that gefitinib, erlotinib and afatinib are ideal drugs for NSCLC patients carrying EGFR mutations.

Original languageEnglish
Pages (from-to)489-497
Number of pages9
JournalCancer Treatment Reviews
Volume39
Issue number5
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Afatinib
  • Chemotherapy
  • Epidermal growth factor receptor
  • Erlotinib
  • Gefitinib
  • Mutations
  • Non-small cell lung cancer
  • Personalized medicine
  • Targeted therapy
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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