How to use EGFR-TKI in clinical practice

Abstract

EGFR-TKIs are recommended as the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations in Japanese and Western guidelines. Although there has been no evidence of direct comparison between each TKI (gefitinib, erlotinib, and afatinib), we must select a proper agent from the viewpoint of risk-benefit balance for each patient in clinical practice. Regarding the efficacy, the type of mutation became important according to results from LUX-Lung 3&6. Afatinib is recommended for young (<75 y.o.) Del19 patients with good performance status (PS) based on positive results from two independent subgroup analyses. On the other hand, gefitinib or elrotinib are still suitable for patients with L858R. Elderly patients should be treated with first-generation TKIs due to insufficient evidence of afatinib for them. Some retrospective studies suggest a high efficacy of erlotinib against carcinomatous meningitis, which should be evaluated in prospective studies. From the safety point of view, gefitinib is safer than erlotinib and afatinib except for hepatotoxicity, thus it is recommended even for patients with PS3-4 in Japanese guideline. Afatinib causes severer diarrhea, skin rash, and paronychia than first-generation TKIs, which requires appropriate medication and dose modification. Regarding interstitial lung disease, each TKI seems to have similar risk and some risk factors suggested from previous large cohort studies should be considered. Although some studies demonstrated promising results of combined regimen such as erlotinib plus bevacizumab or gefitinib plus chemotherapy, they should not be used in clinical practice until their efficacy is confirmed by phase III studies. Adding chemotherapy on TKI beyond disease progression is also investigational and not recommended in clinical practice. Meanwhile, re-challenge of TKI for patients who previously benefited from TKI may be a reasonable option in a later-line setting.