Nov 19 2007
Genentech, Inc. has announced that both study arms of a randomized, multi-center Phase II clinical study of Avastin (bevacizumab) administered alone or in combination with irinotecan chemotherapy demonstrated encouraging six-month progression-free survival (PFS) and objective response rate in patients with relapsed glioblastoma multiforme (GBM), the most common and aggressive type of brain cancer.
As assessed by independent radiological review, 36 percent (31/85) of GBM patients treated with Avastin alone, and 51 percent (42/82) of patients treated with Avastin in combination with chemotherapy, lived without the disease advancing within six months. No new or unexpected safety events related to Avastin have been observed in the study. The data were presented at the 12 th Annual Scientific Meeting of the Society for Neuro-Oncology.
“ Historical estimates suggest that only 15 percent of patients with this aggressive type of brain cancer live without their cancer progressing within six months, ” said Timothy Cloughesy, M.D., director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles and lead investigator for the study. “ 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. ”
“ These findings exceeded our expectations, and due to the high unmet medical need of patients with relapsed GBM we plan to discuss these data with the FDA to determine next steps, ” said Hal Barron, M.D., Genentech's senior vice president, Development and chief medical officer.
According to the American Cancer Society (ACS), the five-year survival rate for patients with GBM is 3 percent, and has not changed in more than 25 years. The ACS estimates there will be 20,500 new cases of brain cancer and 12,740 brain cancer deaths in 2007.
Study Results
In addition to six-month PFS rates of 36 and 51 percent respectively in the Avastin-alone and Avastin plus chemotherapy arms, preliminary estimates of tumor response were observed in 21 percent (18/85) of patients treated with Avastin alone and in 34 percent (28/82) of patients treated with Avastin in combination with chemotherapy.
Adverse events related to Avastin in this trial appeared to be similar to those previously reported in other studies of Avastin. The most common severe (Grade 3 or greater) toxicities in the Avastin alone arm were hypertension (8 percent, 7/84) and convulsion (6 percent, 5/84). The most common severe adverse events in the Avastin plus chemotherapy arm were convulsion (13 percent, 10/79) and neutropenia (9 percent, 7/79). Grade 1 and 3 intracranial hemorrhage occurred in two patients in the Avastin alone arm, and one patient in the Avastin plus chemotherapy arm experienced a Grade 4 intracranial hemorrhage. There were two deaths associated with adverse events in the Avastin alone arm and one death associated with an adverse event in the Avastin plus chemotherapy arm.
Study Design
The study was a Phase II, open-label, multicenter, randomized, non-comparative study that enrolled 167 patients with GBM whose cancer had relapsed after first- or second-line therapy. All patients had received prior temozolimide. Patients were randomized to receive Avastin alone or in combination with irinotecan every other week for up to 104 weeks. The primary endpoints were six-month PFS and objective response rate as determined by an Independent Radiology Facility (IRF). PFS was defined as the absence of any event of cancer progression or death. Secondary endpoints of the study included overall survival and safety. The study is ongoing and final analyses for safety and other efficacy endpoints will be available in 2008.
About Avastin
Avastin is a therapeutic antibody designed to specifically inhibit vascular endothelial growth factor (VEGF), a protein that plays an important role in angiogenesis and the maintenance of existing blood vessels throughout the lifecycle of a tumor. By inhibiting VEGF, Avastin is designed to interfere with the blood supply to a tumor, which is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information on angiogenesis, visit http://www.gene.com. For full prescribing information and Boxed Warnings on Avastin, visit http://www.avastin.com.
The FDA first approved Avastin on February 26, 2004, as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Avastin is also indicated in combination with intravenous 5-FU-based chemotherapy for second-line treatment of patients with metastatic carcinoma of the colon or rectum. On October 11, 2006, the FDA approved Avastin in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer. Avastin is being studied worldwide in more than 300 clinical trials in 20 different tumor types.
Avastin Safety
Avastin has a well-characterized safety profile in its approved indications. The most serious adverse events associated with Avastin across all trials were GI perforation, wound healing complications, hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), neutropenia and infection, nephrotic syndrome and congestive heart failure. The most common adverse events in patients receiving Avastin were asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis and proteinuria.
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