AFATINIB IN THE TREATMENT OF METASTATIC AND LOCALLY ADVANCED LUNG ADENOCARCINOMA WITH EGFR MUTATIONS: NEW SIDES STUDIED POSSIBILITIES

Abstract

A reasonable strategy for drug therapy of non-small-cell lung cancer (NSCLC) with activating mutations of EGFR is the use of tyrosine kinase inhibitors (TKI) in front-line therapy, providing a two-fold increase in life expectancy for patients with metastatic or locally advanced form of the disease. The results of several randomized trials determined and proved the role of Afatinib, the selective irreversible inhibitor of protein kinase receptors of the ErbB family, which consists in the following positions: a verifiable increase in progression-free period (PFP) as front-line metastatic EGFR-mutated NSCLC as compared to chemotherapy, regardless of the EGFR gene mutation type; the advantage in respect of overall survival (OS) as front-line therapy with frequent EGFR gene mutation in NSCLC, with Del19 in particular (OS increase by more than 1 year in comparison with chemotherapy); the advantage in progression-free survival (PFS), treatment time duration (TTD) as well as in objective response rate (ORR) in comparison with Gefitinib against metastatic EGFR-mutated NSCLC; therapeutic efficacy against brain metastasis and many rare mutations; dose adjustment of Afinitib with a view of its tolerability is an effective measure to decrease the drug-induced toxicity rate without affecting its therapeutic efficacy. This article also presents the results of clinical and economic research of the response and benefit of comparable drugs (Afatinib, Gefitinib and Erlotinib) for treatment of patients with NSCLC in the Russian Federation and the results of minor studies demonstrating the new opportunities of Afinitib and its combinations with other «partners». In particular, the efficiency of Afinitib use in the treatment of patients with HER2-mutated lung cancer is provided. In addition, the safety and efficacy of combinations of Afatinib + Bevacizumab and Afatinib + Cetuximab after the formation of acquired resistance to TKI is also noted, which can be used as a therapeutic option in case of Т790М mutation. Current controversial issues concerning the effectiveness of this drug with the new and other rare mutations, the allegedly incomplete cross-resistance against the previous two drugs of this group, lack of information about the therapeutic benefit of Afinitib in case of discordancy of the primary tumor and its metastasis call for further clinical research studies and refinement of diagnostic tests and systems.

Keywords

• locally advanced and metastatic non-small cell lung cancer
• adenocarcinoma of the lung
• tyrosine kinase inhibitors of egfr
• egfr-activating mutations
• targeted therapy
• resistance
• afatinib