First- and Second-Generation EGFR-TKIs Are All Replaced to Osimertinib in Chemo-Naive EGFR Mutation-Positive Non-Small Cell Lung Cancer?

• Published in: International journal of molecular sciences Vol. 20; no. 1; p. 146
• Main Authors: Takeda, Masayuki, Nakagawa, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.01.2019; MDPI
• Subjects: Acrylamides; Adenocarcinoma; Aniline Compounds; Antibodies, Monoclonal - therapeutic use; Bevacizumab; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Chemotherapy; drug resistance; Drug Resistance, Neoplasm; epidermal growth factor receptor (EGFR); Epidermal growth factor receptors; ErbB Receptors - genetics; Gefitinib; Humans; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Monoclonal antibodies; Mutation; Non-small cell lung carcinoma; non–small cell lung cancer (NSCLC); Piperazines - therapeutic use; Progression-Free Survival; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Randomization; Review; Studies; Targeted cancer therapy; Tumors; Tyrosine; tyrosine kinase inhibitor (TKI); Vascular endothelial growth factor; Japan; mutation; drug resistance; non–small cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR); tyrosine kinase inhibitor (TKI)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20010146

Activating mutations of the epidermal growth factor receptor gene ( ) are a driving force for some lung adenocarcinomas. Several randomized phase III studies have revealed that treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) results in an improved progression-free survival (PFS) compared to standard chemotherapy in chemonaive patients with advanced non⁻small cell lung cancer (NSCLC), selected based on the presence of mutations. Patients treated with second-generation EGFR-TKIs have also shown an improved PFS relative to those treated with first-generation EGRF-TKIs. Osimertinib is a third-generation EGFR-TKI that still irreversibly inhibits the activity of EGFR after it has acquired the secondary T790M mutation that confers resistance to first- and second-generation drugs. Its efficacy has been validated for patients whose tumors have developed T790M-mediated resistance, as well as for first-line treatment of those patients with mutation⁻positive NSCLC. Although there are five EGFR-TKIs (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) currently available for the treatment of -mutated lung cancer, the optimal sequence for administration of these drugs remains to be determined. In this review, we addressed this issue with regard to maximizing the duration of the EGFR-TKI treatment.