Targeted Therapies Expand Options for Servicemembers, Dependents With Brain Tumors

AUSTIN, TX — For decades, standard care for most primary brain tumors changed little: Surgery to remove what could be extracted safely, radiation when surgery wasn’t option or following surgery and a short list of chemotherapies that were often nearly as hard on patients as the tumors themselves. That is finally shifting, according to Tim Gregory, MD, an Army neuro-oncologist at Madigan Army Medical Center in Tacoma, WA, who presented new data on targeted therapies in neuro-oncology at the Association of VA Hematology/Oncology annual meeting in Austin, Sept. 11-13.

“We have been at a loss for a lot of FDA approvals in neuro-oncology for many years. Our standards of care have not changed a whole lot except for recent approvals in targeted therapies,” Gregory told U.S. Medicine ahead of his talk, “Precision Medicine in Neuro-Oncology: Integrating Targeted Therapies in a Military Practice Setting.” “It’s opened up a lot of opportunities for patients who ordinarily didn’t have good surgical options, and we often prefer to spare them conventional treatments like radiation. Now we can offer them targeted therapies in some really exciting settings.”

Many targeted therapies for brain tumors are oral medications aimed at specific molecular drivers, an approach Gregory said makes them easier for patients to tolerate and easier for him to deliver to servicemembers and their dependents wherever they might be.

A Shrinking Specialty, a Widening Reach

The need is significant. Gregory’s presentation drew on a mapping analysis that identified 263 neuro-oncologists certified by the United Council for Neurologic Subspecialties to treat adults nationwide, a civilian total, he noted, that still leaves much of the U.S. without patients having a dedicated brain tumor specialist in driving distance. Nearly 70% of those neuro-oncologists, 183 of 263, practice in the 10 best-served states, while 12 states have none at all. Since the analysis was done, the number of practicing neuro-oncologists nationally has risen to roughly 300, but the geographic mismatch persists. “The East Coast has a lot of really great centers. California has some great centers, but it truly is a desert in the Pacific region,” Gregory said.

That discordance is more acute inside the military health system. Gregory’s mentor, Brett Feeler, MD, who practiced at Walter Reed National Military Medical Center, retired this summer, leaving Gregory as the only neuro-oncologist on active duty. A former resident recently began a neuro-oncology fellowship at UCSF and will be available to share the workload in two years. In the meantime, Gregory single-handedly covers a vast service area that has him treating patients by telehealth in Anchorage and Fairbanks, AK; Honolulu; South Korea; and American Samoa, among other locations, while coordinating labs and imaging locally through case managers and pharmacists.

“That’s been a really exciting part of building my practice the last three years,” Gregory said. Colleagues and co-residents keep him hopping. “I just keep getting all these referrals from Pacific locations. If I can establish with a good case manager and a good pharmacist, and I can do labs and MRIs, I can see these patients virtually and really broaden the care we can provide.”

The IDH Mutation and a New Standard for Low-Grade Glioma

The clearest example of the shift enabled by targeted therapies, Gregory said, involves mutations in isocitrate dehydrogenase (IDH), the most common driver of low-grade gliomas, such as grade 2 astrocytomas and oligodendrogliomas, in adults. Median survival for glioblastoma, an IDH-wild-type grade 4 tumor, remains 15 to 18 months. Grade 4 astrocytomas that carry an IDH mutation, by contrast, carry a markedly better prognosis, with median survival of 2 to 5 years.

That biology recently translated into a new treatment option through the phase III INDIGO trial, which tested the oral IDH1/2 inhibitor vorasidenib against placebo in patients with residual or recurrent grade 2 glioma. The trial was unblinded in March 2023 after an independent data monitoring committee found early evidence of efficacy, making it the first positive phase III trial in low-grade glioma since 2016. Median progression-free survival was 27.7 months with vorasidenib compared with 11.1 months with placebo (HR 0.39). Median time to next intervention had not been reached in the vorasidenib arm at the data cutoff, vs, 17.8 months for placebo (HR 0.26). At 24 months, 83% of patients on vorasidenib had not required a next intervention, compared with 27% on placebo. Vorasidenib is now incorporated into NCCN guidelines and into the VA’s oncology clinical pathway for IDH-mutant astrocytoma.

The appeal of targeted therapies in most cases, Gregory said, is time. “I don’’t really think of them as curative so much as we’re calming down a pathway and hoping for slow volume reduction of the tumor,” he said. “The main role of vorasidenib is delaying the time to needing one of those big interventions like radiation. If we can just keep them stable on that drug for as long as possible, that pushes down the road when they’re going to have to undergo a more aggressive form of conventional therapy.” That delay matters, he added, because radiation, while still the backbone of treatment for high-grade tumors, can carry cognitive consequences a decade or more later, a particular concern for patients expected to be long-term survivors.

Two cases from Gregory’s practice illustrate how targeted therapy is used, both close to home and at a distance. A 38-year-old active-duty submariner, a regional patient close enough to see Gregory in clinic, experienced 11 months of intermittent right arm and leg numbness before a corpsman, alarmed by a new speech disturbance during the episodes, ordered an MRI of the cervical spine that detected up a brain lesion. After subtotal resection confirmed an IDH-mutant grade 2 astrocytoma, serial imaging on vorasidenib has shown the tumor dramatically shrinking. Halfway around the Pacific, a 42-year-old woman with a small residual tumor of the same type has been stable on vorasidenib for a year of entirely virtual care in American Samoa overseen by Gregory from Tacoma through the military’s teleoncology system.

Not every tumor responds as well. Diffuse midline gliomas, a more aggressive and diffusely infiltrating category of tumor, typically do not show a durable benefit from targeted therapy even when a molecular target is present, Gregory said. “Whether it’s completely durable is not always the case,” he said. “But if we can sustain neurologic function and quality of life, that’s what we’re trying to do.”

Vorasidenib is only one piece of what Gregory described as a broader shift toward molecularly guided care in neuro-oncology. At AVAHO, he illustrated that shift with additional cases involving MEK and BRAF inhibitors in inherited tumor disorder neurofibromatosis (NF1). He also discussed an ALK inhibitor borrowed from lung cancer to treat other types of neurofibromatosis and dordaviprone, which received accelerated FDA approval in 2025 for H3K27M-altered diffuse midline glioma.

For now, Gregory wants oncologists across the military health system to know that, “Every patient is unique, and we can individualize their treatment now,” based on the tumor profile, not just its location. “In the modern era, there are more options than just the older surgical and radiation options, and even beyond conventional chemotherapy,” for patients with brain tumors, he said. Targeted therapies enable a “level of precision that has made a huge difference across oncology.”

 

1. Gregory, T, MD. September 10, 2026. Precision Medicine in Neuro-Oncology: Integrating Targeted Therapies in a Military Practice Setting [Slides]. Association of VA Hematology/Oncology annual meeting, Austin, TX,