Dacomitinib for the first-line treatment of patients with EGFR-mutated metastatic non-small cell lung cancer

Mariacarmela Santarpia, Jessica Menis, Imane Chaib, Maria Gonzalez Cao, Rafael Rosell

Research output: Contribution to journalReview article

Abstract

Introduction: Different EGFR tyrosine kinase inhibitors (TKIs) are currently approved for the first-line treatment of NSCLC patients with EGFR mutations. Dacomitinib is an orally administered, second-generation pan-HER inhibitor that has shown to improve PFS and OS compared to the first-generation TKI gefitinib and is the most recent inhibitor to be approved in this setting. Areas covered: This article will review relevant literature regarding preclinical findings and clinical data from phase I-III trials of dacomitinib. We particularly discuss the mechanism of action of dacomitinib and its clinical efficacy and toxicity as a novel, first-line therapeutic option for EGFR-mutated NSCLC. Expert commentary: The therapeutic landscape for EGFR-mutated NSCLC has been greatly expanded. In the first-line setting, we have currently first-, second- and third-generation EGFR TKIs available and some combination strategies, including EGFR TKIs with anti-angiogenic drugs or chemotherapy, have also shown to be effective. However, more data are needed to define the optimal therapeutic sequencing of all these targeted agents and combinations. In this view, molecular profiling of tumor tissues and liquid biopsies may provide novel insights on mechanisms of resistance to different drugs and guide treatment decisions.

Original languageEnglish
Pages (from-to)831-840
Number of pages10
JournalExpert Review of Clinical Pharmacology
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 2019

Keywords

  • Antineoplastic Agents/administration & dosage
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Drug Resistance, Neoplasm
  • ErbB Receptors/genetics
  • Humans
  • Lung Neoplasms/drug therapy
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasm Metastasis
  • Progression-Free Survival
  • Quinazolinones/administration & dosage
  • Survival Rate

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