Protein kinase inhibitors to treat non-small-cell lung cancer

Abstract

Introduction: Activating mutations of the EGFR and rearrangement of anaplastic lymphoma kinase (ALK) best illustrate the therapeutic relevance of molecular characterization in NSCLC patients.

Areas covered: For this review article, all published data on the most relevant Phase III trials with tyrosine kinase inhibitors (TKIs) for the treatment of NSCLC were collected and analyzed.

Expert opinion: Eight Phase III trials clearly established EGFR TKIs as the best therapeutic option for front-line therapy in EGFR-mutated patients. In pretreated NSCLC, EGFR TKIs are considered more effective than standard monotherapy with cytotoxics in presence of classical EGFR mutations, whereas in the EGFR wild-type population, a similar efficacy to docetaxel or pemetrexed in term of survival has been demonstrated. In ALK-translocated NSCLC, a Phase III trial demonstrated the superiority of a multi-target TKI, including ALK, in terms of progression-free survival, response rate and toxicity profile when compared to standard second-line chemotherapy. New agents targeting EGFR or ALK are under evaluation particularly in individuals with acquired resistance to EGFR TKIs or crizotinib.

Keywords::

• afatinib
• crizotinib
• erlotinib
• gefitinib
• NSCLC

Declaration of interest

This manuscript is supported by the Italian Association for Cancer Research IG 2012 – 13157, Fondazione Ricerca Traslazionale and Istituto Tumori Toscano Project F13/16. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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