Afatinib: emerging next-generation tyrosine kinase inhibitor for NSCLC

fatinib: emerging next-generation tyrosine kinase inhibitor for NSCLC Review (653) Total Article Views Authors: Nelson V, Ziehr J, Agulnik M, Johnson M Published Date March 2013 Volume 2013:6 Pages 135 - 143 DOI: http://dx.doi.org/10.2147/OTT.S23165 Received: 01 September 2012 Accepted: 10 October 2012 Published: 05 March 2013 Valerie Nelson, Jacqueline Ziehr, Mark Agulnik, Melissa Johnson Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA Abstract: The discovery of epidermal growth-factor receptor (EGFR)-activating mutations and the introduction of oral EGFR tyrosine kinase inhibitors (EGFR-TKIs) have expanded the treatment options for patients with non-small cell lung cancer. The first two reversible EGFR-TKIs, erlotinib and gefitinib, are approved for use in the first-line setting in patients with known EGFR-activating mutations and in the second- and third-line settings for all NSCLC patients. These first-generation EGFR-TKIs improve progression-free survival when compared to chemotherapy in patients with EGFR-activating mutations in the first-line setting. However, nearly all patients develop resistance to EGFR-directed agents. There is a need for further therapy options for patients with disease progression after treatment with reversible EGFR-TKIs. Afatinib is an irreversible ErbB family blocker that inhibits EGFR, HER2, and HER4. In vitro and in vivo, afatinib have shown increased inhibition of the common EGFR-activating mutations as well as the T790M resistance mutation when compared to erlotinib and gefitinib. Clinically, afatinib has been evaluated in the LUX-Lung series of trials, with improvement in progression-free survival reported in patients with EGFR-activating mutations in both first- and second-/third-line settings when compared to chemotherapy. Further investigation is needed to determine the precise role that afatinib will play in the treatment of patients with non-small cell lung cancer and EGFR-activating mutations.