Novel method for preventing brain metastases may be ‘paradigm-changing’ if successful

Vascular endothelial growth factor and immune checkpoint inhibitors may help prevent brain metastases among patients with solid tumors, according to results from a systematic review and meta-analysis published in Neurology.

“As treatment for the most common solid tumors (and lymphoma) are improving dramatically in the era of immune checkpoint and molecularly targeted therapy, the central nervous system is rapidly becoming the most common site of disease relapse and treatment failure,” Michael Glantz, MD, from the departments of neurosurgery, neurology and oncology at Penn State Milton S. Hershey Medical Center in Pennsylvania, told Healio Neurology.

“While we have made modest advances in treating brain metastases, particularly with stereotactic radiosurgery, relapse is the rule, the treatments themselves often convey substantial neurologic toxicity and all treatments are mostly palliative,” Glantz continued. “Preventive therapy has been largely uninvestigated.”

Glantz and colleagues sought to evaluate the impact of vascular endothelial growth factor (VEGF) and immune checkpoint inhibitors as prophylaxis for brain metastasis development. They searched four databases between Jan. 1, 2000, and June 1, 2020, for randomized controlled trials of adults with systemic cancer that reported incidence of brain metastases treated with and without VEGF inhibitors. They also looked for observational studies of adults with systemic cancer that reported incidence of brain metastases treated with and without immune checkpoint inhibitors. No randomized controlled trials evaluated the role of immune checkpoint inhibitors among this patient population. The researchers used a binary random-effects model to estimate pooled relative risks (RR).

The investigators analyzed data from seven studies of VEGF inhibitor use and incidence of new brain metastases that included a total of 6,212 patients with breast, colon and non-small cell lunger cancer. Meta-analysis revealed a lower incidence of new brain metastases among those treated with a VEGF inhibitor compared with control participants (RR = 0.71; 95% CI, 0.56-0.89). A search for immune checkpoint inhibitors and incidence of new brain metastases revealed eight studies that included a total of 732 patients with non-small cell lung cancer or metastatic melanoma, where immune checkpoints inhibitors served as adjunctive therapy to radiosurgery.

Meta-analysis revealed those treated with immune checkpoint inhibitors had a lower incidence of out-of-treatment-field brain metastases compared with control participants at 1 year (RR = 0.65; 95% CI, 0.49-0.88). The researchers noted high and moderate overall Grading of Recommendations, Assessment, Development and Evaluations framework score for the role of bevacizumab and immune checkpoint inhibitors, respectively.

According to Glantz, he and colleagues are preparing to open a formal prospective trial to determine whether they can corroborate the findings of the current study.

“A successful approach to prophylaxis, if it was logistically tolerable and not associated with prohibitive toxicity, would, potentially, be paradigm-changing,” Glantz said.