Afatinib (Giotrif®) is a dual receptor tyrosine kinase (RTK) inhibitor, which selectively and irreversibly blocks receptors of the ErbB family. By downregulating the ErbB signalling, afatinib inhibits tumour growth. Currently, afatinib is approved both in the US and Europe for the treatment of TKI naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations. However, afatinib has not yet received marketing authorisation for the treatment of erlotinib/gefitinib refractory NSCLC patients, who have progressed on afatinib after initial benefit, neither in the US nor in Europe.

The combined use of afatinib and paclitaxel for this indication has been investigated in the LUX–Lung 5 trial, a randomised, open-label phase III study. 202 pre-treated patients were randomised to receive either afatinib–paclitaxel or single agent chemotherapy. The stratification of randomisation was based on the duration of benefit on previous gefitinib/afatinib treatment and sex. The primary outcome of the study was progression-free survival (PFS). For patients treated with afatinib–paclitaxel, median PFS was significantly longer compared to the chemotherapy group (5.6 vs 2.8 months). In contrast, median overall survival (OS) did not differ between the two tested groups (p = 0.994). In terms of safety, treatment-related adverse events (AEs) of any grade as well as of grade 3–5 were more common in the afatinib–paclitaxel group compared to the chemotherapy group. The most frequent AEs in the afatinib–paclitaxel arm were diarrhoea, alopecia, asthenia, decreased appetite, and rash.

Although the study shows a significant gain in median PFS, the treatment with afatinib–paclitaxel is associated with a higher expanse of AEs and relatively high costs. In addition, more data will be required due to the unexpected low number of enrolled patients and the subsequent lower power of the study.