Optimal sequencing strategies in the treatment of EGFR mutation–positive non–small cell lung cancer: Clinical benefits and cost-effectiveness

PURPOSE: To summarize current understanding of the efficacy, role, and cost-effectiveness of the available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and to evaluate sequencing strategies based on the available evidence. Summary. EGFR TKIs are the current standard of care for patients with EGFR mutation–positive non–small cell lung cancer (NSCLC). Five EGFR TKIs are currently approved in the United States for use in a first-line setting; these TKIs differ in mechanism of action, efficacy, safety, and cost. Most patients develop resistance to first-line EGFR TKIs and require subsequent therapy with additional EGFR TKIs, chemotherapy, and/or other targeted agents. A major consideration when selecting EGFR TKIs, both as first-line or subsequent treatment options, is cost-effectiveness. Although clinical trials have shown that the second- and third-generation EGFR TKIs are superior in efficacy to the first-generation agents, pharmacoeconomic studies suggest that the first-generation agents are the most cost-effective, with the second-generation TKI afatinib also considered cost-effective in some studies. Despite its impressive efficacy, osimertinib appears to be less cost-effective due to substantially higher acquisition costs. CONCLUSION: Preliminary data suggest that first-line afatinib followed by osimertinib may offer promising survival outcomes and, on the basis of efficacy alone, may represent an optimal sequencing strategy in the majority of patients with EGFR mutation–positive NSCLC, in particular Asian patients and those with Del19-positive tumors. However, considerably more research into outcomes and costs associated with consecutive sequencing of EGFR TKIs is needed before any conclusions can be reached.