Phase II trials of Avastin (bevacizumab) for the treatment of aggressive brain cancer have shown promising results, said Genentech, makers of the drug, who presented their findings at the 12th Annual Scientific Meeting of the Society for Neuro-Oncology that took place between 15th and 18th November, in Dallas, Texas.
Avastin (bevacizumab) is a monoclonal antibody that inhibits the growth of tumours by blocking the production of new blood vessels (angiogenesis) that would feed the tumour. The drug, which has been described as a “blockbuster” cancer drug, was one of the first clinically available angiogenesis inhibitors in the US.
Given alone or with irinotecan chemotherapy in a randomized, multi-center, phase II trial, the drug showed an encouraging six-month progression-free survival (PFS) and objective response rate in patients with the most common and aggressive type of brain cancer, relapsed glioblastoma multiforme (GBM).
According to the American Cancer Society (ACS), only 3 per cent of patients with GBM survive longer than 5 years, and this figure has not altered in 25 years. The Society estimates that in 2007 there will be 20,500 new cases of brain cancer and 12,740 brain cancer deaths in the US.
36 per cent (31 out of 85) patients treated with Avastin alone, and 51 per cent (42 out of 82) treated with Avastin combined with chemotherapy, lived without the disease advancing within six months, reported Genentech, who said the results were “assessed by independent radiological review”.
Genentech researchers said they observed no new or unexpected safety events related to Avastin.
Dr Timothy Cloughesy, lead researcher of the study, and director of the Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (UCLA) said that:
“Historical estimates suggest that only 15 percent of patients with this aggressive type of brain cancer live without their cancer progressing within six months.”
“The findings suggested that at six months, more patients had lived without their cancer advancing when Avastin was administered as a single-agent or in combination with chemotherapy, than what we would normally expect,” he added.
In this phase II, open-label, multicenter, randomized, non-comparative study, Cloughesy and colleagues enrolled 167 patients with GBM whose cancer had relapsed. They were randomized to either an Avastin alone or Avastin with irinotecan chemotherapy group, and all patients had received prior temozolimide. The treatment was administered every other week for up to two years (104 weeks).
The main outcome measure was PFS, which was defined as the “absence of any event of cancer progression or death”. The researchers also assessed overall survival and safety.
As well as the six-month PFS rates of 36 and 51 per cent in the Avastin only and Avastin with chemotherapy groups, the results also showed that:
- Preliminary estimates of tumour response were seen in 21 per cent (18 of 85) of patients treated with Avastin only.
- The figure for Avastin with chemotherapy was 34 per cent (28 out of 82).
- Adverse events linked to Avastin were similar to previous trials.
- The most common severe (grade 3 or higher) toxicities in the Avastin only group were: hypertension (8 per cent), and convulsion (6 per cent).
- The figure for the Avastin plus chemotherapy group were: convulsion (13 per cent) and neutropenia (9 per cent); neutropenia is a condition where there is a low count of neutrophils, a type of white blood cell.
- Grade 1 and grade 3 intercranial (brain) hemorrhage occurred in 2 participants in the Avastin only group.
- One patient had a grade 4 hemorrhage in the Avastin plus chemotherapy group.
- Two deaths were linked to adverse events in the Avastin only group, and one in the Avastin plus chemotherapy group.
So far, the findings have turned out better than the researchers expected and have prompted the company to spur efforts to discuss the findings with the US Food and Drug Administration (FDA) and find out what the next step should be in getting the drug to this new group of patients.
The trial is still ongoing and final figures for safety and other efficacy results will be available in 2008, said the researchers.
Avastin was first approved by the FDA in February 2004, to treat metastatic colorectal cancer in combination with chemotherapy. Since then it has been approved for particular types of lung cancer. There are currently over 300 trials worldwide assessing the drug’s potential to treat over 20 different types of tumour.
Written by: Catharine Paddock