Class act: Safety comparison of approved tyrosine kinase inhibitors for non-small-cell lung carcinoma

Mauricio Burotto*, Syed Abbas Ali, Geraldine O'sullivan Coyne

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Introduction: The past decade has seen the development and widespread use of tyrosine kinase inhibitors (TKIs) targeting a mutated EGFR (mEGFR) for the treatment of metastatic NSCLC. We discuss the main properties of the TKIs currently recommended for the treatment of mEGFR NSCLC: gefitinib, erlotinib and afatinib.Areas covered: The mechanism of action, pharmacodynamics and pharmacokinetics of these drugs, with emphasis on the historical context of their preclinical and clinical development, will be covered, including potential resistance mechanisms to these first-generation TKIs that has driven the trial design for second and third generations of EGFR inhibitors. Six Phase III clinical trials comparing these three TKIs with cisplatin-based chemotherapy upfront for mEGFR NSCLC provide the basis for the comparative safety and toxicity analysis between these agents. Class-related toxicity of these EGFR inhibitors, including life-threatening effects, will be discussed.Expert opinion: Toxicity and safety analysis from the Phase III trials of these agents in mEGFR populations suggests that afatinib has more frequent and severe side effects. Given that an efficacy advantage has not yet been demonstrated for afatinib over erlotinib and gefitinib, the consistent class toxicity profile of these agents means that gefitinib and erlotinib are a safer first-line treatment recommendation.

Original languageEnglish
Pages (from-to)97-110
Number of pages14
JournalExpert Opinion on Drug Safety
Issue number1
StatePublished - 1 Jan 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Informa UK, Ltd.


  • Afatinib
  • Clinical trial
  • Erlotinib
  • Gefitinib
  • Mutated EGFR
  • Safety
  • Toxicity
  • Tyrosine kinase inhibitor


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