Afatinib (BIBW 2992) development in non-small-cell lung cancer.

Afatinib (BIBW 2992), a novel aniline-quinazoline derivative, irreversibly and equipotently targets the intrinsic kinase activity of all active ErbB receptor family members. Preclinical results show that afatinib is effective in lung cancer models, including those with EGF receptor (EGFR) mutations resistant to reversible first-generation EGFR inhibitors. Afatinib is being investigated in the LUX-Lung program, which will evaluate afatinib as a first-line treatment in patients with EGFR-activating mutations (LUX-Lung 2, 3 and 6) and as a second- or third-line treatment in patients that have acquired resistance to gefitinib and/or erlotinib (LUX-Lung 1, 4 and 5). LUX-Lung 1 and 2 have demonstrated, within their respective target groups, a significant increase in the disease control rate of 58 and 86%, respectively, and significant prolongation of progression-free survival. Further Phase III clinical trials are currently ongoing to assess afatinib in combination with paclitaxel (LUX-Lung 5), and compared with cisplatin/pemetrexed (LUX-Lung 3) or cisplatin/gemcitabine (LUX-Lung 6).