[More Personalized Treatment using Diversified Molecular Targeted Therapy Strategies for EGFR Mutation-Positive Non-Small-Cell Lung Cancer-Sequential Treatment Comprising First- and Second-Line Therapy with EGFR-TKIs and Treatment Options in Combinat

For epidermal growth factor receptor(EGFR)gene mutation-positive advanced non-small-cell lung cancer, molecular targeted therapy with EGFR tyrosine kinase inhibitors(EGFR-TKIs)is the mainstay of treatment. In Japan, 5 EGFR-TKIs[gefitinib and erlotinib(first-generation), afatinib and dacomitinib(second-generation), and osimertinib(third-generation)]have been approved, and only ramucirumab, an anti-angiogenic agent, has been approved for use in combination with the first-generation EGFR-TKIs. Since only osimertinib is approved for use in second-line therapy in the patients with confirmed T790M mutation after EGFR-TKI treatment, any other EGFR-TKI than osimertinib has to be selected as the first-line therapy of sequential treatment using EGFR-TKIs both as first-line and second-line therapy. Treatment options vary widely, and it is therefore important to select an optimal treatment based on clinical information such as a subtype of the EGFR gene mutation, as well as the patient's preference to potentially use molecular targeted therapy for second-line therapy. This article outlines clinical study data on the use of EGFR-TKIs as first- and second-line therapies and the use in combination with anti-angiogenic agents. It also describes our clinical experience with a successful shift from first-line therapy with an EGFR-TKI to second-line therapy with EGFR-TKI in sequential treatment.