Afatinib in the first-line treatment of epidermal-growth-factor-receptor mutation-positive non-small cell lung cancer: a review of the clinical evidence

Abstract

First-line afatinib significantly improved progression-free survival, patient-reported outcomes, and quality of life compared with chemotherapy regimens in patients with advanced epidermal-growth-factor-receptor (EGFR) mutation-positive non-small cell lung cancer, based on results of the LUX-Lung 3 and LUX-Lung 6 trials. When the analysis of these trials was restricted to patients with common EGFR mutations only (exon 19 deletions and L858R), the advantage over chemotherapy was even more pronounced. A significant overall survival advantage was firstly demonstrated versus chemotherapy in patients with non-small cell lung cancer-harboring EGFR exon 19 deletion (del19) mutations. First-line afatinib was also effective in patients with certain uncommon EGFR mutation and patients with central nervous system metastasis. So far, these data are not sufficient to conclude that afatinib is better than first-generation EGFR inhibitors. In addition, the toxicity profile of afatinib was somewhat worse than that observed with either erlotinib or gefitinib. In the absence of direct comparisons, for each patient the choice among the available EGFR inhibitors should take into account all the clinically relevant endpoints, including disease control, survival prolongation, tolerability, and quality of life.

Keywords: EGFR mutation; afatinib; first-generation EGFR-TKI; non-small cell lung cancer.

Figure 1.

Summary box of LUX-Lung trials with afatinib in non-small cell lung cancers. Red box: clinical trials in EGFR mutation-positive patients; Blue box: clinical trials in unselected patients Cis, cisplatin; Pem, pemetrexed; Gem, gemcitabine; Chemo: chemotherapy.

Figure 2.

The frequency of grade ⩾ 3 adverse events including rash, diarrhea, hepatotoxicity and interstitial lung disease. ILD, interstitial lung disease, AEs, adverse events.