The risk of CNS bleeding was a major concern upon the introduction of anti-angiogenic therapies and resulted in the frequent exclusion of brain metastasis patients from clinical trials [
5,
12]. However, several subsequent studies proved that there is no increased safety issue, as frequency of bleeding as well as other side effects were not accumulated in brain metastasis patients [
12‐
14]. In line with this, the rate of bevacizumab-related adverse events was similar among patients with (21%) and without (20%) brain metastases [
15]. Nevertheless, due to the systematic exclusion of brain metastases patients in the majority of phase III trials, only limited knowledge on the efficacy of anti-antigenic therapies in brain metastasis patients is available [
5].
Some phase II trials as well as retrospective analyses investigated the efficacy of bevacizumab-based treatments in patients with asymptomatic NSCLC brain metastases (Table
1) [
15,
16]. Here, intracranial response rates of bevacizumab in combination with carboplatin and paclitaxel (61.2%) or in combination with erlotinib (12.5%; unselected cohort) similar to the expected extracranial response rate were observed [
16]. Median progression-free survival ranged from 6.3 to 6.7 months and overall survival from 12 (erlotinib combination; unselected for EGFR status) to 16 (carboplatin and paclitaxel combination) months, and was therefore shown to be similar between patients without brain metastases and patients with asymptomatic brain metastases [
15‐
17]. For most other entities, only case reports or small case series have focused on the efficacy of anti-angiogenic therapies. Progression-free survival after treatment with paclitaxel and bevacizumab ranged from 6 to 11 months in a case series of five patients with breast cancer brain metastases [
18]. A case series of 16 patients suffering from newly diagnosed, untreated brain metastases from renal cell carcinoma treated with first-line sunitinib presented with a median time to progression of 2.3 months, a median overall survival of 6.3 months, and an overall good tolerability of sunitinib [
19]. Similarly, analysis of the expanded access program of sunitinib in renal cell carcinoma brain metastasis patients (
n = 231) revealed a median progression-free survival of 5.6 months and a median overall survival of 9.2 months [
20]. Further, some case reports also suggest a clinical efficacy in the rare event of colorectal carcinoma brain metastases. Here, a median overall survival of 20.6 months (range 7–42 months) after bevacizumab-based treatment was observed in patients with colorectal brain metastases (
n = 5) [
21].