FIRST LINE AVASTIN PROMISING IN GLIOBLASTOMA

NEW YORK (Reuters Health) Dec 17 - Adding bevacizumab to standard first-line treatment for glioblastoma multiforme (GBM) may improve progression-free survival, a new single-arm phase II study demonstrates.

However, it's still not clear whether administering bevacizumab with initial therapy improves overall survival compared to when it's used at recurrence only, Dr. Albert Lai of the University of Los Angeles, David Geffen School of Medicine, and his colleagues conclude.

Bevacizumab, which targets vascular endothelial growth factor, has shown promise in treating recurrent GBM, Dr. Lai and his team note in a December 6 online report in the Journal of Clinical Oncology.

To investigate whether adding the drug to adjuvant radiotherapy and temozolomide - the current first-line standard of care - would benefit patients as well, Dr. Lai and his team enrolled 70 patients newly diagnosed with GBM. All received standard radiotherapy within three to six weeks of surgery along with daily temozolomide and biweekly bevacizumab.

Once radiotherapy was complete, the patients were given temozolomide for five days every four weeks, and continued to take bevacizumab biweekly.

Overall survival and progression-free survival were 19.6 and 13.6 months, respectively.

Among a control cohort of 110 patients treated with radiation and temozolomide at the University of California, Los Angeles/Kaiser Permanente Los Angeles, overall survival was 21.1 months and progression-free survival was 7.6 months. And in the 287-patient phase III trial that initially established temozolomide plus radiation therapy as first-line treatment (by the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada), overall and progression-free survival were 14.6 and 6.9 months, respectively.

MGMT promoter methylation was correlated with improved overall and progression-free survival, the researchers found, while there was some evidence that patients with the worst prognosis gained the most benefit from first-line bevacizumab. Toxicity in the current study was comparable to that seen in past studies.

Two large randomized phase III trials are now underway to determine if first-line bevacizumab does provide an overall survival advantage, Dr. Lai and his team write. "If confirmed, these findings would have significant economic impact by sparing the cost of approximately 15 additional treatments," they note.

Many glioblastoma drugs fail in randomized phase III trials after showing promise in single-arm phase II studies, Dr. Eric T. Wong of Harvard Medical School in Boston and Dr. Stephen Brem of the H. Lee Moffitt Cancer Center & Research Institute in Tampa warn in an editorial accompanying the study. "Despite favorable findings, there is still insufficient evidence to warrant the routine clinical practice of adding bevacizumab to initial temozolomide and radiotherapy for newly diagnosed glioblastoma," they conclude.

J Clin Oncol. Posted December 6, 2010. Abstract