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Antiangiogenic treatments prolong OS in glioblastoma subgroup
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A subgroup of patients with glioblastoma and highly vascularized tumors experienced an OS that was about 1 year longer when given targeted antiangiogenic treatments, according to a Stanford University School of Medicine retrospective study published in Neuro-Oncology.
These results come after two large, phase 3 clinical trials published in The New England Journal of Medicine concluded that the antiangiogenic bevacizumab (Avastin, Genentech) conferred no survival benefit in patients with glioblastoma.
“Traditionally, patients with glioblastoma are given a diagnosis based on the histology of their tumor, and then assigned a grade and a stage,” Daniel Rubin, MD, associate professor of biomedical data science, radiology and medicine at Stanford School of Medicine, said in a press release. “But this information is not always specific enough to clearly inform treatment. We’ve developed a new method of classifying glioblastoma by quantitatively analyzing the MRI that is routinely performed during diagnosis.”
glioblastoma each year. It is the most common and most aggressive brain cancer in adults, with a median survival of about 15 months after diagnosis. Until recently, clinicians treated the brain tumor with antiangiogenic compounds, like bevacizumab, designed to block the growth of new blood vessels in the tumor, depriving it of oxygen and nutrients.
When those treatments were found to be ineffective in two reports in The New England Journal of Medicine, Rubin and colleagues studied the medical records of 117 patients with glioblastoma. Researchers divided patients into two subgroups based on results of perfusion MRI — those whose tumors were more highly vascularized (n = 51), and those whose tumors were less vascularized (n = 66).
Rubin and colleagues discovered that highly vascularized tumors expressed more genes involved in blood vessel growth and in protecting cells from hypoxia, and thus were significantly more likely to benefit from treatment with antiangiogenic therapies than less vascularized tumors.
Among patients in the highly vascularized group, those who were treated with antiangiogenic therapies experienced a longer median survival compared with those not given antiangiogenic therapy (552.5 days vs. 178 days; HR = 0.28; P = 0.22). Overall, the median survival for patients treated with antiangiogenic therapy was 439 days compared with 546 says for those not given antiangiogenic therapy.
“The most exciting finding was that those members in the highly vascularized group who had received antiangiogenic treatment lived significantly longer — on average more than a year — than others in the same group who did not get antiangiogenic therapy,” Rubin said.
This analyses was performed using perfusion MRIs, which already exist as part of the diagnostic procedure for glioblastoma.
“Our findings speak to the fact that the biology of glioblastoma can vary significantly among individuals, and that certain subgroups of patients may benefit from treatments that appear ineffective when screened across a large unselected mix of patients,” Rubin said.
Researchers noted the small number of patients with complete treatment information as a limitation to their study, adding that future large-cohort prospective studies evaluating the effectiveness of antiangiogenic treatments with elevated perfusion-weighted imaging features would be helpful to confirm their results.
“This is a turning point,” Rubin said. “We believe we can identify those people who are likely to benefit from antiangiogenic treatments, and also begin to think outside the box to identify other types of therapies for those who are unlikely to respond. This shows that subtyping cancers like glioblastoma can have a huge impact on how we treat the disease.” – by Chuck Gormley
Disclosure: Researchers reported no relevant financial disclosures.
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