AbstractBackgroundThe efficacy and safety of osimertinib combined with bevacizumab in non‐small cell lung cancer (NSCLC) patients with brain metastasis harboring epidermal growth factor receptor (EGFR) mutations have not been fully studied.MethodsTreatment‐naïve NSCLC patients with brain metastasis harboringEGFR‐activating mutations were treated with osimertinib 80 mg oral daily and bevacizumab 15 mg/kg intravenously on day 1, repeated every 21 days, until disease progression, intolerable toxicity, or death. The primary endpoint was the median progression‐free survival (mPFS), and the secondary endpoints were the median overall survival (mOS), response rates, and toxicities. This study has been registered inClinicalTrials.gov(NCT05104281) and is ongoing.ResultsA total of 52 Chinese patients were enrolled, of whom 17 harboredEGFR19 del and 35 harboredEGFRL858R mutation. The objective response rate (ORR) was 75.0% and the disease control rate (DCR) was 96.2%; the mPFS was 17.0 months (95% CI: 11.46–22.54), while the mOS was not reached. The mPFS was 20.0 months (95% CI: 14.56–25.44) and was 17.0 months (95% CI: 13.28–20.72) for patients harboringEGFR19 del andEGFRL858R mutation (p= 0.844), respectively. The intracranial ORR was 82.7%, and the intracranial mPFS was 22.0 months (95% CI: 2.92–41.08).The main adverse events were mild‐to‐moderate hand‐foot syndrome, diarrhea, hypertension, and proteinuria. Three patients developed grade III proteinuria, while five patients developed grade III hypertension; they permanently discontinued bevacizumab treatment.ConclusionsOsimertinib combined with bevacizumab shows promising results inEGFR‐mutated NSCLC patients with brain metastasis, and the side effects are tolerable.