How to use afatinib in clinical practice

Abstract

Afatinib is an irreversible inhibitor that demonstrated superior progression‐free survival time over pemetrexed (or gemcitabine) and cisplatin in EGFR mutation positive lung adenocarcinoma in two randomized phase III studies. In patients with del 19 in exon of EGFR, afatinib had an overall survival advantage over 1 year over patients started with chemotherapy in both studies. Afatinib has also demonstrated activity in uncommon EGFR mutation in prospective studies. Activity of afatinib in the brain was also clearly demonstrated in the above studies. Therefore, afatinib is indicated for all EGFR mutation positive patients with the exception of only patients with exon 20 insertion or high T790M mutation. Diarrhea, skin rash, especially acneform rash, paronychia and mucositis are the main side effects of afatinib. Diarrhea should be treated with adequate loperamide and hydration. Skin side effects can be treated with antibiotics and local treatment. However, it is also important to apply caution for sun exposure to reduce side effects. If patients cannot tolerate side effects, dose reduce from 40 mg per day to 30mg and further to 20 mg per day is recommended. We recently analyzed patients who had dose reduced to 30 mg or 20 mg in the previous phase III studies. Although dose reduction occurred in 53% of the patients and majority (86%) of those occurred within the first 6 months. Side effects were reduced dramatically. The plasma level of afatinib after dose reduction was the same compared to those patients without dose reduction. Patients who had dose reduction had a median PFS of 11.3 months versus 11 months for those who did not reduce the dose. We concluded that dose reduction may not affect the efficacy of afatinib and can improve the tolerability of patients to afatinib treatment. Thus dose reduction of afatinib should be considered as long as is it performed according to observed side effect of afatinib. Afatinib at 30 mg can also be combined with weekly paclitaxel safely in the later line treatment. Tolerability‐guided dose adjustment of afatinib is an effective measure to reduce treatment‐related adverse events without reducing therapeutic efficacy.