Avastin approved for aggressive brain tumour
Roche has gained US approval for Avastin in people with the aggressive brain cancer glioblastoma multiforme (GBM).
The drug can now be used in patients whose disease has progressed following prior therapy.
The new indication was granted under the FDA’s accelerated approval programme because there are few treatment options against GBM, which currently proves deadly very quickly.
The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted unanimously for approval on 31 March.
“People with this type of brain cancer have had no new treatments in more than a decade,” said Timothy Cloughesy, M.D., director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. “After so many years with little progress in this field, Avastin was associated with a durable tumour response and doctors now have a new medicine to offer patients.”
“Today’s approval would not have been possible without the dedication of physicians, patient advocates, the FDA and most importantly the people who participated in the clinical trials and their families who had the courage to support them,” said William Burns, chief executive of Roche's pharmaceuticals division. “A global phase III trial in patients with newly diagnosed glioblastoma will soon begin enrollment to further evaluate Avastin in this setting.”
The National Brain Tumor Society, an American patient group, has welcomed the FDA’s accelerated approval of Avastin. “A brain cancer diagnosis is devastating because the tumours invade brain tissue and can cause rapid deterioration,” said Harriet Patterson, director of patient services for the National Brain Tumor Society. “Until now, people with relapsed glioblastoma have had almost no treatment choices and little hope.”
Following initial treatment with chemotherapy and radiation, more than 90% of patients with glioblastoma will see their cancer return and there are few effective treatments when the initial therapy stops working. Median survival following progression of this cancer is approximately six months.
The effectiveness of Avastin for this aggressive form of brain cancer is based on an improvement in objective response rate from the BRAIN study (AVF3708g) and an NCI study (NCI 06-C-0064E). There is currently no data available from randomised controlled trials to demonstrate an improvement in disease-related symptoms or increased survival with Avastin in glioblastoma.
Roche is awaiting a decision in Europe, after filing an application with the EMEA in December 2008.
The BRAIN Study
The accelerated approval is based on independently reviewed data from the BRAIN study which was an open-label, multicentre, non-comparative Phase II study that included 167 patients with glioblastoma whose disease had progressed following initial treatment with temozolomide and radiation.
Patients were randomised into two arms: Avastin alone or Avastin in combination with irinotecan. A primary endpoint of the study was objective response rate
In the 85 patients treated with Avastin alone, the study showed:
- In 26% (95% confidence interval: 17.0%, 36.1%) of patients tumour response was observed;
- In patients where tumour response was observed, half experienced a response of at least 4.2 months (95% confidence intervals: 3.0 months, 5.7 months)
The second co-primary endpoint was six month progression-free survival (PFS); overall survival and safety were also evaluated.
The median age of the patients treated with Avastin alone was 54 years. Additionally, 32% were female, 81% were in first relapse, 45% had a Karnofsky performance status (KPS) of 90 to 100 and 55% had a KPS of 70 to 80. Patients with active brain haemorrhage were excluded from the study.
The most frequently reported adverse events in patients treated with Avastin alone were fatigue (45%), headache (37%), high blood pressure (30%), diarrohea (21%) and nose bleeds (19%). There were two deaths possibly associated with adverse events in the group of patients treated with Avastin alone.
Glioma (cancer of the glial cells) is the most common type of malignant primary brain tumour, accounting for approximately one third of all cases diagnosed. Glioblastoma multiforme is the most common and most aggressive type of glioma. The prognosis for patients with GBM is poor, and generally depends on the success of surgery to remove the tumour.
Glioblastoma affects approximately 10,000 people per year in the United States. Following initial treatment, glioblastoma tumours nearly always return and currently, there are limited treatment options for patients when these relapses occur. According to historical estimates, less than 10% of patients with recurrent GBM respond to treatment, and approximately 15% will live six months without their disease getting worse.