Osimertinib combined with bevacizumab as the first‐line treatment in non‐small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations

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 http://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.

Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer

“… 38 , 39 In addition, several studies have shown that bevacizumab has promising results in NSCLC patients with brain metastases. 38 , 40 – 42 In addition, we performed subgroup analyses of cancer types and brain metastases between the AT and non-AT groups and found that there was no significant difference in COVID-19 outcomes between the two groups ( Figure 6 ). Thus, although the ratio of cancer types and brain metastases was not balanced between the two groups, it had no significant effect on the outcome of COVID-19.…”

Comparison of osimertinib plus bevacizumab against osimertinib alone in NSCLC harboring EGFR mutations: a systematic review and meta-analysis

“…Indeed, clinical studies have shown promising activity against central nervous system metastases from combination modality. 27 , 28 Given these thoughts, we conducted a pooled analysis based on BM. The results showed that the combination treatment yielded a mild trend of better PFS in those patients with BM (HR = 0.91, 95% CI: 0.46–1.77), though not reaching statistical significance.…”

Myofibrillogenesis Regulator‐1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin‐Protein Ligase Itchy Homolog in the Metastasis of Non‐Small Cell Lung Cancer

“…And non‐small cell lung cancer (NSCLC) is the main type of cancer in lung cancer, accounting for ≈85–90% of all cases. [ 1 , 2 , 3 , 4 ] For radical surgical treatment of lung cancer, only a small number of patients diagnosed with early lung tumors can accept. Moreover, the risk of postoperative recurrence is high.…”