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AACR: Targeted Agent Boosts Survival in Brain Cancer
By Charles Bankhead, Staff Writer, MedPage Today
Published: April 20, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
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Action Points
Explain to patients that treatment with a targeted drug called trabedersen improved survival in a certain type of brain cancer compared with treatment with conventional chemotherapy.
Note that the targeted agent has orphan-drug approval but is not widely available.
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
WASHINGTON -- Patients with recurrent or refractory anaplastic astrocytoma lived almost twice as long when treated with an investigational targeted agent than with standard therapy in a randomized clinical trial reported here.
Patients treated with low-dose trabedersen, an inhibitor of transforming growth factor-beta 2 (TGF-β2), had a median overall survival of 39.1 months compared with 21.7 months for those who received conventional chemotherapy.
Twice as many patients were alive at two years when treated with the investigational agent than with standard therapy.
"Trabedersen is safe and has a clear clinical benefit in high-grade glioma," Piotr Jachimczak, MD, of Antisense Pharma in Regensberg, Germany, said during a press briefing at the American Association for Cancer Research meeting.
"Some patients have had complete resolution of brain tumors for as long as eight years," he added.
Overall, patients with grade IV glioblastoma had similar survival with trabedersen or chemotherapy, although younger patients did substantially better with the TGF-β2 inhibitor.
Several types of tumors overexpress TGF-β2, including high-grade gliomas. The overexpression is associated with several key factors involved in tumor progression, including evasion of immune response; migration, invasion, and metastasis; angiogenesis and neovascularization; and proliferation.
Trabedersen is an antisense oligonucleotide that selectively downregulates production of TGF-β2.
The agent is being investigated for treatment of several aggressive cancers and has received orphan-drug designation from the European Medicines Agency and the FDA for use against pancreatic cancer and high-grade gliomas.
Trabedersen is delivered directly into the tumor with an internal catheter and an external portable pump and subcutaneous infusion line.
Jachimczak said the method of administration avoids problems related to crossing the blood-brain barrier. The delivery system causes little interference with daily activities, and patient acceptance has been good, he added.
Jachimczak reported findings from a phase IIb study involving 134 patients with high-grade gliomas: 95 with grade IV glioblastoma and 39 with grade III anaplastic astrocytomas.
The patients were randomized to three treatment groups: trabedersen 10 μM or 80 μM or standard chemotherapy with either temozolomide (Temodar) or the combination of procarbazine, CCNU, and vincristine.
Patients in the trabedersen arms received as many as 11 cycles of therapy, administered as seven days on treatment followed by seven days off per cycle.
Patients with anaplastic astrocytomas had a two-year survival of 83% with the lower dose of trabedersen compared with 53% for the higher dose of the investigational agent and 41% for standard therapy.
Jachimczak, who spoke to reporters by phone during the press briefing, was among millions of airline passengers whose flights were canceled as a result of the volcanic activity in Iceland.
He said trabedersen and chemotherapy led to similar outcomes in patients with glioblastoma. However, a prespecified analysis showed that patients younger than 55 had a two-year survival of 40% with trabedersen compared with 13.3% for the control arm.
On the basis of the phase II results, a phase III clinical trial has begun, comparing the lower dose of trabedersen and standard chemotherapy in patients with recurrent or refractory anaplastic astrocytoma.
The study was supported by Antisense Pharma.
Jachimczak is an employee of Antisense Pharma.
Primary source: American Association for Cancer Research
Source reference:
Jachimczak P, et al "Targeted therapy of high-grade gliomas using the TGF-beta2 inhibitor trabedersen (AP12009): Results of the phase IIb study as basis for the phase III SAPPHIRE study" AACR 2010; Abstract 3716.