Clinical Benefits Associated with First Line Treatment Using Afatinib

Iwama Eiji, Okamoto Isamu

doi:10.2482/haigan.55.866

Three types of EGFR-TKIs (epidermal growth factor receptor-tyrosine kinase inhibitors) such as gefitinib, erlotinib and afatinib are available for the treatment of EGFR mutation-positive lung cancer patients in Japan. Afatinib is an irreversible HER family (EGFR, HER2, HER4) blocker. Although treatment with this drug has a substantial clinical benefit, the frequency of adverse effects (AEs) such as rash, paronychia and diarrhea is high and management of these AEs is important. Two phase III studies (LUX-Lung 3, LUX-Lung 6) were performed to compare the efficacy of afatinib and platinum-based chemotherapy in previously untreated lung adenocarcinoma patients with EGFR mutations. Afatinib showed a significantly longer progression free survival (PFS) (primary endpoint) than chemotherapy in these two studies, and the results were similar to those of other clinical studies with first generation EGFR-TKIs (gefitinib, erlotinib). Afatinib also demonstrated a benefit in the overall survival (OS) for exon 19 deletion mutation-positive patients, which was not observed in other studies with first generation EGFR-TKIs. Although the mutation of threonine-790 to methionine (T790M) in EGFR has been reported to be a major cause of resistance to first generation EGFR-TKIs, the resistance mechanism to afatinib has not yet been elucidated. It is important to investigate the mechanisms of resistance to afatinib and to develop new strategies to overcome this problem. We herein summarize the utility of first line treatment with afatinib, while referring the results of both clinical studies and molecular biological studies.

Clinical Benefits Associated with First Line Treatment Using Afatinib

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