Abstract
BACKGROUND: The 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. METHODS: Treatment-naïve NSCLC patients with brain metastasis harboring EGFR-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 in ClinicalTrials.gov (NCT05104281) and is ongoing. RESULTS: A total of 52 Chinese patients were enrolled, of whom 17 harbored EGFR 19 del and 35 harbored EGFR L858R 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 harboring EGFR 19 del and EGFR L858R 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. CONCLUSIONS: Osimertinib combined with bevacizumab shows promising results in EGFR-mutated NSCLC patients with brain metastasis, and the side effects are tolerable.