Roche's Bevacizumab Offers Hope to Brain Cancer Patients

CEBU, Philippines - After over a decade that saw no new effective therapy developed for the most common and aggressive form of brain cancer, Roche’s bevacizumab now offers hope to patients with recurrent or progressive glioblastoma (GBM).

Glioma is the most common type of primary brain tumour, accounting for approximately one third of all cases diagnosed. Glioma also represents around 80 percent of all primary malignant brain tumour cases. Glioblastoma (GBM) is the most common type of glioma.

Glioblastoma affects approximately 17,000 people per year in the EU. Most patients with GBM experience relapse or progression of their disease following initial treatment with surgery, radiation therapy, and chemotherapy. When the disease recurs, prognosis is particularly poor and treatment options are limited.

Prolongs Survival, Prevents Disease Progression

Bevacizumab recently received the Philippine Food and Drug Administration (FDA) approval either as a single agent or in combination with irinotecan (a chemotherapy drug) as treatment for GBM after relapse or disease progression. The Philippine FDA’s approval was based on results of the BRAIN Study (AVF3708g) showing bevacizumab prolonging the survival of patients with GBM without their disease getting worse.

The BRAIN study showed that when bevacizumab was evaluated as a single agent, at six months, almost half (42.6 percent) of GBM patients on bevacizumab lived without their disease getting worse. When bevacizumab was combined with irinotecan, this figure increased to 50.3 percent.

In the study, tumor size in nearly a third (28 percent) of patients on bevacizumab decreased by at least 50 percent. When bevacizumab was combined with irinotecan, this figure increased to 38 percent.

Adverse events in the BRAIN study were consistent with those previously seen with bevacizumab and no new safety signals were reported. In addition, there were low rates of discontinuation of bevacizumab due to adverse events.

 “There have been many clinical trials that have evaluated a wide variety of targeted therapies for GBM, but the only agent that has been shown to be compellingly useful in recurrent GBM is bevacizumab,” said Dr. Marc Chamberlain, Chief, Division of Neuro-Oncology, Seattle Cancer Care Alliance, University of Washington.

Dr. Chamberlain was the keynote speaker during a dinner scientific symposium hosted by Roche Philippines last July 16 at the Makati Shangri-La Hotel, which was attended by local oncologists (cancer specialists), neurosurgeons and neurologists.

Quality Of Life Benefits

Another important finding of the BRAIN Study is that patients who responded to bevacizumab-based therapy also have a stabilization or improvement in neurocognitive function and a reduction in their dose of steroids.

Neurocognitive function includes the ability to think and reason, to make judgments and remember things. A decline in this function, a common consequence of GBM, can be distressing for both patients and their families.

Although steroids are an important part of managing symptoms in many patients with GBM, they can lead to complications such as weight gain, insomnia, and behavioral changes. Reduction in steroid dose means that physicians may be able to reduce the side effects of long-term steroid use.

“Nearly all patients on bevacizumab-based therapy had some reduction in steroid dose, a third was able to come off steroids, and a third had more than 50 percent reduction in steroid dose. This is an enormous quality of life benefit and in itself a compelling reason to use bevacizumab in patients with brain tumors,” said Dr. Chamberlain.

Precise Mode of Action

Bevacizumab works by recognizing and blocking a chemical signal called VEGF sent by brain tumor cells. VEGF stimulates the growth of new blood vessels needed by a tumor to grow and spread (metastasize) to other parts of the body.

“Bevacizumab is highly specific against VEGF and therefore is particularly useful in treating GBM, which has one of the highest VEGF levels among solid tumors,” Dr. Chamberlain explained.

Bevacizumab’s precise mode of action allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments. Bevacizumab helps to control tumor growth and extend survival with only a limited impact on the side effects of chemotherapy.

Combining bevacizumab with chemotherapy creates a two-pronged attack on the brain tumor: chemotherapy prevents tumor cells from multiplying while bevacizumab cuts off the tumor’s source of nourishment thereby starving it.

Warning Signs

“GBM is a tumor that originates from the brain itself as opposed to a tumor from the lung or breast that spreads to the brain,“ said Dr. Roy Torcuator, neurosurgeon and neuro-oncologist, Head of the Comprehensive Brain Tumor Center, St. Luke’s Medical Center Quezon City and Global City. “Its exact cause is unknown. The only known contributory factor is previous radiation exposure, such as head x-rays.”

GBM is common in individuals aged 55 to 65 years mostly among males, and is more commonly seen in developed countries, according to Dr. Torcuator. “It may be underreported in the Philippines.” There are currently no local prevalence data on GBM; in the US, 23,000 cases are reported annually, he added.

“Symptoms are related to increased pressure in the head caused by the tumor and the area of the brain involved,” explained Dr. Torcuator. Common symptoms include headaches, blurring of vision, nausea, vomiting, weakness on one side of the body, speech and balance problems, numbness, and seizures.

Hope for Patients

Prior to the development of bevacizumab there were really no effective drugs against recurrent GBM, Dr. Torcuator said. “This was very frustrating for doctors and certainly devastating for patients and their families. With the availability of bevacizumab, there is renewed hope for patients with recurrent GBM.”

“GBM is very difficult to manage because for a long time no new drugs were available that could give physicians an edge over this disease. We therefore welcome the new indication for bevacizumab as treatment for recurrent GBM,” said Dr. Dennis Tudtud, President, Philippine Society of Medical Oncology (PSMO).

“Bevacizumab has transformed the management of GBM,” said PSMO Vice President Dr. Jhade Peneyra. (PR)