Abstract
BACKGROUND: About 25%-40% of people with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) experience brain metastases, which cause major challenges in their treatment. There continues to be no agreement on the ideal method for using EGFR- tyrosine kinase inhibitors (TKIs) and radiotherapy in management. AIM: To systematically assess how effective and safe EGFR-TKIs are when used together with or without radiotherapy in people with EGFR mutation and brain metastases. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a complete literature search was initiated. We selected studies of two designs: Randomized trials and observational studies, which focused on therapies like EGFR-TKIs, radiotherapy, or approaches that combine both. Results for primary outcomes focused on how long people lived without the cancer spreading, whether the brain tumor shrank, and how safe the treatment was. RESULTS: Ten randomized controlled trials and 17 observational studies, totaling 14955 patients, met the inclusion criteria. Osimertinib and similar third-generation EGFR-TKIs performed better in the brain, helping patients with central nervous system (CNS) responses of 60% to 91%. Treatment involving combined EGFR-TKI medicine and radiotherapy worked better for local control and survival than EGFR-TKI treatment alone, mainly in patients with less than three brain metastases, ECOG 0-2, and moderate to severe neurological symptoms. Cognitive function was preserved better in those who received stereotactic radiosurgery and EGFR-TKIs than in those who had whole-brain radiation therapy. CONCLUSION: Third-generation EGFR-TKIs have good CNS effects in EGFR-mutated NSCLC. Treatments that include radiotherapy are sometimes used together, and choosing the right method depends on the amount of cancer, its effect on the person, and patient factors, which includes brain metastases (e.g., > 3), performance status (e.g., ECOG 0-2), and severity of the symptom (e.g., moderate to severe neurological symptoms).