Afatinib in advanced non-small-cell lung cancer

Afatinib is an orally available irreversible blocker of the ErbB family of receptors, including the EGF receptor (EGFR). The EGFR mutations are detectable in 10-15% of western patients diagnosed with advanced non-small-cell lung cancer. In a large, randomized, Phase III registration trial (LUX-Lung 3), afatinib showed an improvement in progression-free survival compared with pemetrexed/cisplatin as first-line treatment in EGFR mutation-positive advanced non-small-cell lung cancer patients, with significant advantages in objective response, quality of life and symptom control. In a second randomized trial limited to Asian patients (LUX-Lung 6), afatinib significantly prolonged progression-free survival compared with cisplatin/gemcitabine in the same setting. The most common toxicities observed with afatinib are diarrhea, stomatitis and skin rash; these adverse events are frequently described, but are generally reversible, manageable and rarely lead to treatment discontinuation. As of October 2013, afatinib is approved by the US FDA and by the EMA. The LUX-Lung 3 and 6 trials were part of a larger clinical development program in patients with advanced non-small-cell lung cancer, which is summarized in this review.