Role of osimertinib plus brain radiotherapy versus osimertinib single therapy in EGFR-mutated Non-Small-Cell Lung Cancer with brain metastases: a meta-analysis and systematic review

: Single-agent osimertinib has improved outcomes in EGFR-mutated lung cancer patients with brain metastases (BMs), but still, 40% of them will experience an intracranial progression. We performed a systematic review to evaluate the role of brain radiotherapy upfront plus osimertinib. We evaluated articles comparing the use of osimertinib versus osimertinib plus brain radiotherapy. We included 897 patients from nine retrospective studies. Patients treated with combination therapy had an improvement in intracranial progression-free survival (HR 0.76; 95% CI 0.61-0.94) and overall survival (HR 0.56; 95% CI 0.36-0.87) with an acceptable safety profile. Osimertinib with upfront brain radiotherapy may be a suitable first-line treatment option for EGFR mutated patients with BMs at diagnosis. The main limitations of this analysis are the retrospective nature and the inability to control for a single variable of interest. Despite that, the combination of osimertinib and upfront brain radiotherapy is a treatment strategy that deserves further prospective trials.