Avastin After Recurrence in Glioblastoma Shows No Benefit

Continuing Avastin (bevacizumab) in patients with recurrent glioblastoma after progression of the disease does not improve patient outcomes, according to results from the phase 2 CABARET trial.¹ The results were presented by Elizabeth J. Hovey, from the Prince of Wales Hospital in Sydney, Australia, during the 2015 annual meeting of the American Society of Clinical Oncology (ASCO), a gathering of nearly 30,000 oncology professionals in Chicago.

Avastin 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 [Avastin] in recurrence,” says Timothy F. Cloughesy, 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 says that offering Avastin 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 Avastin 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 Avastin at recurrence and progression by answering two questions: whether or not adding carboplatin to Avastin benefited patients with a recurrence and whether or not patients benefited from continuing Avastin 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 Avastin or Avastin alone. The part 1 results,² which were presented at ASCO in 2013, found no progression-free survival (PFS) or overall survival (OS) benefit to the combination therapy compared with Avastin alone at six months. Final results of part 1 are in press, Hovey says.

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

The part 2 results presented by Hovey¹ showed no PFS, OS, or radiologic benefit to continuing Avastin after progression. The median PFS in the Avastin group was 1.8 months compared with 2.0 months in the cease Avastin group. Median OS was 3.4 months versus 3.0 months. 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 Avastin and those who did not, Hovey says. However, there were slightly higher rates of adverse events in the Avastin arm.

“There were minimally high rates of toxicity in the [Avastin] arm,” she says.

Hovey says 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 [Avastin] 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 Avastin after progression was beneficial. He says her data should finally debunk the idea that flare-ups routinely occur after Avastin discontinuation in patients whose disease has progressed.

“The data are really compelling,” he says.

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.