Brain Trust: Cutting-Edge Treatments for Glioblastoma on the Rise

New treatments, such as immunotherapy, are continuing to prove successful for patients with glioblastoma, one of the most dangerous cancers.
ARLENE WEINTRAUB
PUBLISHED: MARCH 01, 2016
Talk about this article with other patients, caregivers, and advocates in the Brain cancer CURE discussion group.
Ryan DeGrand has had no sign of glioblastoma since he started taking the experimental targeted vaccine Rintega (rindopepimut) more than 10 years ago. PHOTO BY ERIN STUBBLEFIELD
Ryan DeGrand has had no sign of glioblastoma since he started taking the experimental targeted vaccine Rintega (rindopepimut) more than 10 years ago. PHOTO BY ERIN STUBBLEFIELD

Ryan DeGrand was 33 years old and married with two young children when he started suffering debilitating headaches in 2004. The diagnosis, stage 4 glioblastoma, didn’t offer much hope — the standard regimen of surgery, chemotherapy and radiation might buy him a year, his doctors in St. Louis told him. So after he completed the treatment, he got on the Internet and began looking for research centers that specialized in treating his type of brain tumor. 

That search brought him to Duke University, where researchers were in the early stages of testing a vaccine that targets EGFRvIII — a genetic abnormality of the epidermal growth factor receptor (EGFR) that occurs in about one-third of glioblastoma patients and that’s associated with tumor growth and resistance to therapy. The condition is not inherited, but arises from an acquired mutation. DeGrand’s tumor tested positive for the mutation, and he was entered into the trial. 

Today, DeGrand is cancer-free and still on the vaccine, which is a series of four shots in the upper thigh that he receives once a month. “For my family, I was willing to try anything,” says DeGrand, who has started a sporting goods business and welcomed a third child since entering the trial. “I just got my MRI, and everything is clean. I’m living every day to its fullest.

About 15 percent of brain cancers are GBMs, aggressive tumors that rarely spread to other organs but that do grow rapidly inside the brain. They typically cause headaches and nausea, but if they’re located near the brain’s most critical structures, they can also trigger memory loss, weakness and speech problems. Their prevalence increases with age; only about 3 percent of childhood brain cancers are GBMs. Scientists have not yet figured out what causes this type of brain tumor.

The standard therapy for GBM starts with surgery to remove as much of the tumor as possible, as well as to pinpoint the stage of the disease, and to identify genetic markers that might point to personalized treatments. Patients then typically receive radiation and the chemotherapy drug temozolomide. Although this regimen can be very effective at shrinking the tumors, it can cause side effects like nausea, hair loss and headache. The GBMs tend to recur within a median time of seven months, and median survival time is about 15 months, although there is considerable variation. 

Tackling Tumor Variations 

GBMs contain a wide mix of cell types that often differ from patient to patient and even within an individual patient’s tumor, and that vary widely in their response to treatment. What’s more, when they recur after treatment, “the molecular profile of the cancer changes dramatically,” says Mark Gilbert, a senior investigator and chief of the Neuro-Oncology Branch at the National Cancer Institute. “And the further away the recurrence is from the primary tumor, the less alike it is to its parent.” Such variability in GBM tumors “makes treating them incredibly complicated,” he adds.

That’s why drugs that enable the immune system to recognize GBM tumors as enemies — and then destroy them — are considered especially promising. One of the leading contenders is the vaccine that saved DeGrand’s life, Rintega (rindopepimut), which is completing phase 3 trials (Editor's note on March 10, 2016: Despite excitement, the drug did not meet expectations in a phase 3 trial).

Talk about this article with other patients, caregivers, and advocates in the Brain cancer CURE discussion group.
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