Paper Title :EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) after Non-1st-Line Osimertinib Resistance: A Review of EGFR-Dependent Targets of Treatment Options

Author :Donald Y.C. Lie, Paule. Lie, Tam Q. Nguyenand, Lukman Tijani

Article Citation :Donald Y.C. Lie ,Paule. Lie ,Tam Q. Nguyenand ,Lukman Tijani , (2022 ) " EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) after Non-1st-Line Osimertinib Resistance: A Review of EGFR-Dependent Targets of Treatment Options " , International Journal of Advances in Science, Engineering and Technology(IJASEAT) , pp. 38-41, Volume-10,Issue-1

Abstract : Abstract - Lung cancer is the leading cause of cancer-caused death in the world. Of all lung cancer cases, 85% are NSCLC (non-small-cell lung cancer). The Epidermal Growth Factor Receptor (EGFR) is a significant member of the tyrosine kinase type 1 family receptor and about 15%-65% of NSCLC adenocarcinoma is known to express EGFR mutations. EGFR tyrosine kinase inhibitors (TKI) can diffuse across the cell membrane and bind to the ATP binding sites on the kinase interior portion of the EGFR, which can effectively block cellular over-active downstream signaling cascades for treating EGFR-mutant NSCLC. The EGFR TKIs usually result in a significantly longer PFS (Progression-Free Survival) than the traditional platinum-based chemotherapy as the 1st-line treatment for EGFR-mutant NSCLC, and their objective response rate (ORR) is better than chemotherapy and much better than PD-1/PD-L1 immunotherapy checkpoint inhibitors as well. First-generation EGFR TKIs such as gefitinib (Iressa) and erlotinib (Tarceva) weredeveloped first; however, inevitable resistance to the EGFR TKIs will develop after continuous treatment. Therefore, the 2nd-generation EGFR TKIs such as afatinib (Gilotrif) or dacomitinib (Vizimpro) and the third-generation TKI osimertinib (Tagrisso) or HM61713 (Olmutinib), etc. have been developed and approved. Of these EGFR TKIs, osimertinib is now the most popular one in the US as it has shown superior PFS with less toxicity and better brain penetration vs. other TKIs for 1st-line treatmentof EGFR-mutant NSCLC with classic EGFR mutations, and especially for patients who developed acquired T790M mutation from prior EGFR TKIs. Unfortunately, osimertinib resistance still develops on almost all patients, and the resistance mechanisms are diverse and can be rather complex. Therefore, inthis paper, we will focus our discussions on the latest EFGR targeted treatment options for EGFR-mutant NSCLC patients who developed T790M mutation and thentreated with non-1st-lineosimertiniband progressed with various EGFR-dependent mutations and mechanisms. Keywords - EGFR Tyrosine Kinase Inhibitor (TKI), C797S, EGFR (epidermal growth factor receptors), Non-Small-Cell Lung Cancer (NSCLC), Osimertinib Resistance, T790M

Type : Research paper

Published : Volume-10,Issue-1

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