Optimizing therapy sequence to prevent patient attrition in EGFR mutation-positive advanced or metastatic NSCLC

Clinical trial and real-world data in non-small-cell lung cancer indicate that 10-60% of patients that progressed on first- or second-generation EGFR-targeting tyrosine kinase inhibitors (TKI) do not receive systemic second-line therapy. In our article, we discuss efficacy, safety and treatment duration with different EGFR-TKIs and stress the need for delivery of the most efficacious therapy in the first-line. We also provide our perspective on analysis of circulating tumor DNA and the role of EGFR-TKI in combined therapies. Finally, we review new therapeutic options to overcome resistance to EGFR-TKI. We believe that overall treatment duration and access to different medications in subsequent lines of therapy should be considered when planning the optimal treatment strategy. Lay abstract Clinical trial and clinical practice data in non-small-cell lung cancer indicate that 10-60% of patients who no longer respond to initial therapy with EGFR inhibitors, a new type of anti cancer drug, do not receive further treatment. In our article, we discuss the efficacy, safety and treatment duration with different EGFR inhibitors and stress the need for using the most efficacious therapy in the first-line. We also provide our perspective on the analysis of circulating tumor DNA, which is being studied to determine which treatment will be most effective for patients, and the role of combining EGFR inhibitors with other treatments. Finally, we review new therapeutic options to overcome tumor resistance to EGFR inhibitors. We believe that overall duration of initial treatment and access to different medications in subsequent lines of therapy should be considered when planning the optimal treatment strategy.