Abstract

Afatinib: rationale for use in non-small-cell lung cancer based on clinical trail data

Author(s): Allan V Espinosa and Leora Horn

Afatinib is an irreversible ErbB family blocker approved for use as first-line therapy in EGF receptor (EGFR)-positive metastatic non-small-cell lung carcinoma. Its preclinical evaluation showed a higher affinity than reversible tyrosine kinase inhibitors to EGFR-mutated cell lines. This affinity was significantly higher (100-fold) for cell lines expressing the gatekeeper mutation T790M in comparison with EGFR wild-type clones. This article reviews the Phase I studies used to ascertain its safety profile, appropriate dosing and recommended scheduling. A Phase IIb/III trial compared afatinib with placebo in patients who had failed treatment with an EGFR-tyrosine kinase inhibitor and demonstrated an improved response rate and progression-free survival, although no improvement in overall survival. Combination therapy with afatinib and cetuximab has shown promising results. This article also reviews the evidence to support the use of afatinib as a first-line therapy in patients with non-small-cell lung cancer positive for the EGFR mutation exon 19 deletion or L858R point mutation