Bevacizumab After Recurrence in Glioblastoma Shows No Benefit

Elizabeth J. Hovey, MB, BS

Elizabeth J. Hovey, MB, BS

Continuing bevacizumab in patients with recurrent glioblastoma after progression of the disease does not improve patient outcomes, according to results from the phase II CABARET trial.¹The results were presented by Elizabeth J. Hovey, MB, BS, of the Prince of Wales Hospital in Sydney, Australia, at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 2, 2015.

Bevacizumab has become the standard of care for patients with new cases of glioblastoma based on promising clinical trial results, according to Hovey. But in 2009 when the CABARET trial was launched, there were few data to guide treatment decisions after recurrence or during progression.

“We are only beginning to understand more about bevacizumab in recurrence,” said Timothy F. Cloughesy, MD, director of the Neuro-Oncology Program at the University of California-Los Angeles Medical Center, who presented an independent assessment of Hovey’s results.

Despite the uncertainties and a lack of high-level data, Hovey said that offering bevacizumab after a patient has progressed on the drug has become common among oncologists. She explained that clinicians fear a rapid neurologic deterioration or flare-up after discontinuing bevacizumab in these patients, so they continue the therapy.

The independent investigator-initiated CABARET trial was designed to help fill in the lack of data about bevacizumab at recurrence and progression by answering two questions: whether or not adding carboplatin to bevacizumab benefited patients with a recurrence and whether or not patients benefited from continuing bevacizumab after progression.

The trial (ACTRN12610000915055) enrolled 120 patients who had a first recurrence of glioblastoma after treatment with surgery, radiotherapy, or temozolomide. In part 1 of the study, patients were randomized to receive carboplatin plus bevacizumab or bevacizumab alone. The part 1 results,²which were presented at ASCO in 2013, found no progression-free survival (PFS) or overall survival (OS) benefit to the combination therapy compared with bevacizumab alone at 6 months. Final results of part 1 are in press, Hovey said.

In part II of the study, 48 patients with progression were randomized to continue or cease bevacizumab. The patients who continued to part 2 were on average younger and more had a grade II tumor, Hovey said. More than 80% were also taking steroids.

The part II results presented by Hovey¹showed no PFS, OS, or radiologic benefit to continuing bevacizumab after progression. The median PFS in the bevacizumab group was 1.8 months compared with 2.0 months in the cease bevacizumab group (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.59-1.96;P= .81). Median OS was 3.4 months versus 3.0 months (HR = 0.84; 95% CI, 0.47-1.50;P= .56). Hovey noted that given the statistical power of the study it would only be able to detect large differences between the two groups, so smaller benefits could have been missed.

Preliminary analyses of the data found no significant differences in steroid use, radiologic recurrence, or quality of life between the patients who continued bevacizumab and those who did not, Hovey said. However, there were slightly higher rates of adverse events in the bevacizumab arm.

“There were minimally high rates of toxicity in the bevacizumab arm,” she said.

Hovey said the CABARET part 2 results must be put into the context of the overall evidence, some of which has been conflicting. “But this particular study does not support the routine continuation of bevacizumab on disease progression,” she concluded.

Cloughesy applauded Hovey and her colleagues for forthrightly trying to provide an answer to the question of whether or not continued bevacizumab after progression was beneficial. He said her data should finally debunk the idea that flare-ups routinely occur after bevacizumab discontinuation in patients whose disease has progressed.

“The data are really compelling,” he said.

References

1. Hovey EJ. Continuing or ceasing bevacizumab at disease progression: Results from the CABARET study, a prospective randomized phase II trial in patients with recurrent glioblastoma. Presented at: 2015 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2015; Chicago, IL. Abstract 2003.

2. Field KM. A randomized phase II study of carboplatin and bevacizumab in recurrent glioblastoma multiforme (CABARET). Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL. Abstract 2017.