ASCO 2013

Adding bevacizumab to standard first-line chemoradiation for glioblastoma gives no survival benefit

Prof Mark Gilbert - University of Texas MD Anderson Cancer Center, Houston, USA

Glioblastoma is a highly malignant primary brain tumour; the average survival remains less than a year and a half. We have very good data using bevacizumab in recurrent glioblastoma showing a high response rate and prolongation of tumour control so it was very logical to take this treatment into the newly diagnosed setting to see if there would be additional benefit.

What did you do in the different trials?

The trial was a phase III randomised placebo-controlled double blinded study and all the patients underwent three weeks of standard radiation with concurrent temozolomide and at that point were then randomised to receive either radiation, temozolomide and placebo or radiation, temozolomide plus bevacizumab to complete the six weeks of radiation. After the radiation was complete patients would then continue with temozolomide and placebo or temozolomide plus bevacizumab for up to twelve months.

What happened?

Angiogenesis is a major feature of glioblastoma, in fact much of the pioneering work in the 1970s on angiogenesis was done in glioblastoma models. It turns out that the most prominent growth factor in angiogenesis and glioblastoma is VEGF-A and bevacizumab targets VEGF-A and so that was the rationale. The study design, importantly, included a crossover so the patients who were on the placebo arm had the opportunity to get bevacizumab at time of failure. So we really weren’t looking at bevacizumab versus placebo, we were looking at early bevacizumab and, in most patients who chose, opportunity to get bevacizumab as salvage. So the overall survival was not different between the two arms.

Should you use the drug?

I would say that bevacizumab, based on our data which did not show an overall survival improvement using it early, in most patients it should be restricted to the recurrent setting for now. Work is underway to try to find a molecular profile that would distinguish those patients who truly do benefit from early bevacizumab. That work is being done from tumour samples from the OA25 study but even if we have a putative profile it would have to undergo prospective validation before it’s utilised.

What is your take home message for doctors?

My take home message is bevacizumab is an active agent in brain tumours, particularly in glioblastoma, but it can be reserved as a salvage regimen.