Ideal sequencing in Stage IV epidermal growth factor receptor mutant Non朣mall?Cell Lung Cancer
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Date
2022-03
Journal Title
Journal ISSN
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Publisher
Wolters Kluwer - Medknow
Abstract
Evidence from several studies has shown improved progression?free survival (PFS) with first? or second?generation epidermal growth factor receptor (EGFR)杢yrosine kinase inhibitors (TKIs) compared with chemotherapy for advanced NSCLC patients. But resistance to first or second?generation TKI therapies after 9 to 12 months of treatment initiation is a concern. Osimertinib is a third?generation, irreversible, oral EGFR?TKI that potently and selectively inhibits both EGFRm (epidermal growth factor receptor mutated) and EGFR T790M and has demonstrated efficacy in NSCLC central nervous system (CNS) metastases. Trials have reported significantly longer PFS and higher median duration of response with osimertinib compared with first?generation EGFR?TKIs (erlotinib, gefitinib) and chemotherapy, respectively. And relatively lower rates of discontinuation due to adverse events (AEs). Significant improvement in overall survival was also observed when used as first?line treatment. Because EGFR?mutated tumors are highly dependent on EGFR signaling, optimal sequence of available TKIs � erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib � is necessary. The sequencing of EGFR?TKIs has changed over the past decade and depends on factors such as expected efficacy, CNS activity, tolerability, and options available after progression. Third?generation TKI may be the preferred first?line treatment because patients may not opt for or die before the start of second?line therapy, and it is difficult to predict which patients will eventually develop T790M mutation. The favorable tolerability profile alongside a longer time to disease progression makes osimertinib a preferred first?line treatment. Though clinical practice guidelines do not provide clear consensus on the most preferred EGFR?TKI, recent updates recommend osimertinib as a first?line treatment for advanced NSCLC patients. Also, improved patient selection incorporating clinical and molecular characteristics will help translate to better survival outcomes and improved quality of life. This review aims to determine the optimal sequence of administration of the EGFR?TKIs considering toxicity, quality of life, and survival outcomes among advanced NSCLC patients.
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Keywords
Epithelial growth factor receptor mutations, T790M mutation, non杝mall?cell lung cancer, osimertinib, tyrosine kinase inhibitors
Citation
Walia Meenu, Singhal Manish K., Kamle Mangesh S.. Ideal sequencing in Stage IV epidermal growth factor receptor mutant Non朣mall?Cell Lung Cancer. Indian Journal of Cancer . 2022 Mar; 59(1): 80-89