No Benefit to Continued Bevacizumab in Recurrent Glioblastoma

No Benefit to Continued Bevacizumab in Recurrent Glioblastoma

Continuing bevacizumab beyond progression confers no apparent clinical benefit in patients with recurrent glioblastoma compared with cessation of the drug, according to results of the second part of a randomized phase II trial (Abstract 2003).

Elizabeth J. Hovey, MBBS, MSc, of Prince of Wales Hospital, Australia, presented results of the CABARET study during the Central Nervous System Tumors Oral Abstract Session on Tuesday, June 2.

“Offering bevacizumab beyond progression has become relatively commonplace… despite the lack of high-level evidence,” Dr. Hovey said.

The CABARET study was a two-part trial; the first part, presented at the 2013 ASCO Annual Meeting, showed no difference in progression-free survival (PFS) or overall survival (OS) between bevacizumab monotherapy and bevacizumab in combination with carboplatin. The second part, presented on Tuesday, compared continuing bevacizumab to cessation of therapy following disease progression.

A total of 48 patients (40%) continued from part 1 of the trial to part 2; of those, 27 patients (56%) had received bevacizumab monotherapy in part 1, and 21 patients (44%) received bevacizumab/carboplatin. In part 2, 23 patients (48%) were randomly assigned to bevacizumab continuation and 25 patients (52%) to bevacizumab cessation.

Dr. Hovey said there was no evidence of benefit with continuing bevacizumab. The median PFS in the continuation group was 1.8 months, compared with 2.0 months in the cessation group. This yielded a hazard ratio (HR) of 1.08 (95% CI [0.59, 1.96]; p = 0.80). Only one patient in the bevacizumab continuation group passed 6-month PFS (5%), compared with none in the cessation group.

Similarly, the median OS in the continuation group was 3.4 months, compared with 3.0 months in the cessation group, for an HR of 0.84 (95% CI, [0.47, 1.50]; p = 0.55).

Ten of 23 (43%) continuation patients experienced an adverse event (AE) of grade 3 or higher, compared with eight of 24 (33%) cessation patients. There were no AEs causing death in the study, and Dr. Hovey said no AEs were considered unexpected. The bevacizumab continuation group had more AEs total of any grade; 87% of these patients experienced fatigue, compared with 54% of cessation patients, and 30% had any-grade thrombocytopenia, compared with 8% of cessation patients.

There were also several bevacizumab-related AEs, including three patients (13%) in the continuation group with bleeding versus one patient (4%) in the cessation group, as well as single instances in the continuation group of central nervous system hemorrhage, deep vein thrombosis, proteinuria, and abscess; there was one bleeding event in the cessation group. Seventy-eight percent of continuation and 71% of cessation patients had grade 1/2 hypertension.

There were no significant differences with regard to steroid dosing or quality-of-life outcomes.

“This is the first prospective, randomized clinical trial to address the question of bevacizumab continuation in recurrent glioblastoma,” Dr. Hovey said. “Continuing bevacizumab after progression of recurrent glioblastoma did not improve PFS,” nor did it confer “any apparent clinical benefit.” She said that these results must be placed in context with a variety of other data, but this study suggests that bevacizumab should not routinely be continued beyond disease progression.

Discussant Timothy Cloughesy, MD, of the University of California, Los Angeles, called the data compelling. “We have been evaluating bevacizumab for 10 years, and we don’t have a really clear idea of where we’re going,” he said. 

Watch the session: Visit the ASCO Virtual Meeting website.