Effect of erlotinib plus bevacizumab on brain metastases in patients with non-small cell lung cancer

Abstract

Background: The standard therapy for brain metastasis (BM) in non-small cell lung cancer (NSCLC) is radiation therapy (RT), although it is associated with complications such as leukoencephalopathy. In the current report, we retrospectively review data from eight patients who had NSCLC and harbored epidermal growth factor receptor (EGFR) mutations, and who were received erlotinib plus bevacizumab (E+B) as firstline therapy for BM.Methods: Patients were given E+B as first therapy for BM until August 2017 at our institution. Patients receiving local therapy for BM, such as surgery or radiotherapy, were excluded. Patients were administered erlotinib orally (once daily at 150 mg/body) plus bevacizumab by intravenous infusion (15 mg/kg on day 1 of a 21-or 28-day cycle).Results: Eight NSCLC patients who were diagnosed with BM received E+B, including 2 men and 6 women with a median age of 65 years (range, 46-84 years). Four patients had an L858R EGFR mutation, while the other four had an exon 19 deletion. Seven patients had a partial response to E+B treatment, and one had a complete response. The 2-year survival rate was 62.5%. Three patients who were pre-treated with gefitinib had an E+B treatment duration of less than 1 year. At the time of this analysis, four patients had BM-related neurologic symptoms and multiple BMs, and were still receiving E+B with no evidence of treatment failure after more than 1 year.Conclusions: E+B can be used as first-line therapy for BM, even in patients with BM-related neurologic symptoms and multiple BMs.

Phase 1b study of ramucirumab in combination with erlotinib or osimertinib for untreated EGFR-mutated non–small cell lung cancer patients with asymptomatic brain metastases

“…Combination treatment with EGFR-TKIs and antiangiogenic agents has shown a greater e cacy compared with EGFR-TKI monotherapy in patients with EGFR-mutated NSCLC [13,14,20]. The combination of EGFR-TKIs with bevacizumab has also shown encouraging results in EGFR mutation-positive NSCLC patients with brain metastases [30,31]. On the other hand, patients with brain metastases treated with antiangiogenic agents have been thought to be more susceptible to CNS hemorrhage at sites of intracranial lesions because of the occurrence of a fatal cerebral hemorrhage in a phase 1 study [32].…”

Successful Treatment of Combined Large Cell Neuroendocrine Carcinoma Harboring an EGFR Mutation with <b><i>EGFR</i></b>-TKIs plus Bevacizumab: A Case Report

“…Vascular endothelial growth factor produced in the perinecrotic area is thought to be a major cause of both angiogenesis and perilesional edema after radiation therapy to metastatic lesions of the brain [9]. The efficacy and safety of bevacizumab treatment for brain metastasis of NSCLC are well known [10-12], while efficacy of bevacizumab combined with EGFR-TKIs for EGFR -mutated NSCLC with brain metastasis has also been reported [13, 14]. Furthermore, Mairinger et al [15] reported that angiogenesis was also activated to some extent in LCNECs.…”

Metastasis manners and the underlying mechanisms of ALK and ROS1 rearrangement lung cancer and current possible therapeutic strategies

“…122 In addition, there are reports recommending the use of bevacizumab in combination with erlotinib as a rst-line treatment for brain metastases. 123…”