Optimizing outcomes in EGFR mutation-positive NSCLC: which tyrosine kinase inhibitor and when?

Abstract

Despite the efficacy of standard-of-care EGFR tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib and afatinib, in EGFR mutation-positive non-small-cell lung cancer, resistance develops, most commonly due to the T790M mutation. Osimertinib showed clinical activity in the treatment of T790M-positive disease following progression on a first-line TKI, and is approved in this setting. Recently, osimertinib improved efficacy versus first-generation TKIs (erlotinib and gefitinib) in the first-line setting. Multiple factors can influence first-line treatment decisions, including subsequent therapy options, presence of brain metastases and tolerability, all of which should be considered in the long-term treatment plan. Further research into treatment sequencing is also needed, to optimize outcomes in EGFR mutation-positive non-small-cell lung cancer.

Budget impact of sequential treatment with first-line afatinib versus first-line osimertinib in non-small-cell lung cancer patients with common EGFR mutations

“…When patients progress on first-line osimertinib, the most frequent resistance mechanisms are MET amplification (15%) and EGFR C797S mutation (7%) [14]. There are currently no targeted treatment options available after osimertinib and patients failing first-line osimertinib treatment will receive chemotherapy or best supportive care [15,16].…”

Repurposing established cyclic adenosine monophosphate reducing agents for the prevention and therapy of epidermal growth factor receptor inhibitor resistance in non-small cell lung cancer

“…Adenocarcinomas often express activating mutations of the epidermal growth factor receptor (EGFR) and these mutations are predictive of responsiveness to cancer therapy with EGFR tyrosine kinase inhibitors (2). Unfortunately, resistance to these agents always develops due to the formation of additional mutations, of which only one type (EGFR T790M mutation) responds to newer generation EGFR inhibitors (3).…”

Current and Future Molecular Testing in NSCLC, What Can We Expect from New Sequencing Technologies?

“…Numerous targeted therapies have been developed in recent years, particularly in lung cancer [3][4][5][6]. Such therapies changed the standard care for NSCLC stages III and IV from cytotoxic chemotherapies to "specific" first line treatment for selected patients [7]. Initially used in unselected patient populations most targeted drugs failed [3].…”