Ablative Radiotherapy as a Strategy to Overcome TKI Resistance in EGFR-Mutated NSCLC

Simple Summary Most patients with EGFR-mutated NSCLC who receive treatment with targeted therapy will eventually develop resistance, meaning the therapy will lose its efficacy. Prior studies have shown a benefit to continuing to treat patients on TKI therapy despite limited progression of one or more sites of metastatic disease in EGFR-mutated NSCLC. Based on the data reviewed here, the use of radiation therapy to sites of disease progression is both efficacious and carries a low risk for side effects, with the added benefit of allowing patients to continue on TKI therapy. Tyrosine kinase inhibitor (TKI) therapy is the recommended first-line treatment for metastatic non-small-cell lung cancer (NSCLC) positive for epidermal growth factor receptor (EGFR) gene mutation. However, most individuals treated with TKI therapy for EGFR-mutant NSCLC will develop tumor resistance to TKI therapy. Therapeutic strategies to overcome TKI resistance are the topic of several ongoing clinical trials. One potential strategy, which has been explored in numerous trials, is the treatment of progressive sites of disease with stereotactic body radiation treatment (SBRT) or stereotactic radiosurgery (SRS). We sought to review the literature pertaining to the use of local ablative radiation therapy in the setting of acquired resistance to TKI therapy and to discuss stereotactic radiation therapy as a strategy to overcome TKI resistance.