‘Very Promising’: New Cancer Drug, Plixorafenib, Shows Promise For Hard‑to‑Treat Brain Tumors As FDA Speeds Its Development

A Breakthrough Therapy Designation signals the FDA’s commitment to speed the drug’s development for patients with serious, unmet medical needs. It is not yet an FDA approval.

WATCH: What Is Glioma & How Is It Analyzed?

Plixorafenib is an oral therapy designed to shut down cancers driven by abnormal BRAF proteins. It works by blocking mutated BRAF proteins while sparing normal BRAF function, helping slow or stop tumor growth in cancers that rely on these mutations to thrive.

“This designation is a big step for targeted therapies in high‑grade glioma patients with actionable molecular markers,” Dr. Jacob Young, a neurosurgeon at UCSF Health, tells SurvivorNet.

High‑grade gliomas are among the most aggressive brain tumors and typically require a combination of surgery, radiation, and chemotherapy. They are graded on a scale of 1 to 4.

Grade 3 gliomas are considered high-grade and are malignant and fast‑growing. Grade 4 gliomas, such as glioblastoma, are the most aggressive and tend to invade the surrounding brain tissue. These tumors are locally aggressive and require intensive treatment.

For patients whose high‑grade gliomas also carry the BRAF V600E mutation, the disease can be even more challenging. This mutation drives uncontrolled cell growth, but it also creates a potential therapeutic target for cancer drugs designed to stop its proliferation, like plixorafenib.

WATCH: Personalized Medicine and the Tremendous Value of Molecular Testing for Gliomas

To determine whether a glioma carries mutations like BRAF V600E, molecular testing is essential. This testing analyzes the tumor’s DNA to identify specific genetic changes that influence how the tumor behaves and how it can be treated.

“In the past, we treated all gliomas the same way, but molecular testing has changed that,” says Dr. Reid Thompson, Chair of Neurosurgery at Vanderbilt University Medical Center. “Now we can identify specific mutations and tailor treatment to the individual patient.”

Plixorafenib’s Breakthrough Therapy Designation

Plixorafenib was a key focus during phase 1/2a and the ongoing phase 2 FORTE clinical trial.

Data presented at the 2023 Society for Neuro-Oncology (SNO) conference showed that patients with BRAF V600-mutated tumors had a “67% overall response rate” after taking plixorafenib.

“The promising overall response rate reported in the phase 1/2 trial for patients with BRAF V600E-mutated high-grade glioma treated with plixorafenib data is very encouraging,” Dr. Young tells SurvivorNet.

Some of the side effects experienced by patients using plixorafenib included:

• Fatigue
• Nausea
• Diarrhea
• Vomiting
• Liver disruptions (such as inflammation)

“The study demonstrated an improved side effect profile compared with prior alternatives and promising response rates,” says Dr. Juan Pablo Ospina, a neurologist at the University of Pennsylvania Health System.

“Although these findings will require validation in larger clinical trials, the early signals are notable and support the FDA’s designation of plixorafenib as a breakthrough therapy,” Dr. Ospina adds.

These ongoing studies underscore the importance of continued molecular profiling, including next-generation sequencing, which allows scientists and doctors to examine the genetic material (DNA and RNA) in tumor cells “beyond the initial diagnosis,” according to Dr. Ospina.

Molecular Testing of Gliomas

Next-generation sequencing enables the rapid sequencing of genetic material. Simply put, it’s like reading the instruction manual of the tumor at an incredibly detailed level.

Every cell in our body has DNA, which contains genes that serve as instructions for how cells grow and function. In cancer, including gliomas, some of these instructions become faulty due to mutations or other changes in the DNA. These changes can drive tumor growth and affect how a tumor behaves.

Gliomas can look similar under a microscope, but their molecular features are what truly define them. NGS identifies key mutations, such as IDH1/IDH2, that help classify the tumor more precisely and predict how aggressive it may be.

These advanced findings are useful for several reasons, including:

• Personalized Treatment Planning: NGS reveals the genetic changes driving a patient’s tumor, allowing clinicians to tailor therapy. For example, MGMT promoter methylation detected through molecular testing can signal a better response to temozolomide.
• Access to Clinical Trials: Many trials require specific molecular markers. NGS can uncover rare mutations or fusions that make a patient eligible for targeted or experimental therapies they otherwise wouldn’t have access to.
• Monitoring How the Tumor Evolves: Tumors change over time, especially under treatment pressure. Repeat NGS can detect new mutations or resistance mechanisms, helping clinicians adjust therapy as the disease progresses.

What is next-generation sequencing?

Doctors will look for several things in an NGS report, including:

• Gene mutations (IDH1, IDH2, TP53, EGFR)
• Chromosomal changes (1p/19q co‑deletion)
• Gene expression (RNA) patterns
• Tumor mutational burden (TMB)
• Actionable targets (BRAF mutations)

For glioma patients, NGS helps personalize care by revealing the specific genetic features of their tumor. This allows doctors to choose treatments more likely to work and gives patients clearer guidance when considering options, including whether a clinical trial might be a good fit. The added genetic detail helps patients and care teams make more confident, informed decisions.

What To Know About Brain Tumors

Brain tumors can impact a person’s cognitive function and overall well-being, depending largely on the tumor’s size, type, and specific location within the brain. When large enough, tumors may interfere with the central nervous system, pressing on nearby nerves, blood vessels, or tissues. This disruption may result in difficulties with coordination, balance, or mobility.

WATCH: Hope for Glioblastoma Research

While some brain tumors cause noticeable symptoms, others can go unnoticed for long periods.

When symptoms do occur, they might include:

• Persistent headaches
• Difficulty speaking or processing thoughts
• Muscle weakness
• Behavioral or personality changes
• Vision disturbances
• Seizures
• Hearing loss
• Confusion
• Memory issues

According to the National Cancer Institute, brain tumors can also vary greatly in behavior. There are several types of non-cancerous or benign brain tumors, like chordomas, craniopharyngiomas, and gangliocytomas.

Common malignant (cancerous) brain tumors include:

• Gliomas: The most frequent and aggressive form of primary brain cancer
• Astrocytomas: Derived from star-shaped brain cells, with four growth grades
• Ependymomas: Graded based on aggressiveness
• Oligodendrogliomas: Can grow slowly (Grade 2) or aggressively (Grade 3)
• Medulloblastomas: Fast-growing and often found in children
• Glioblastomas: The most common and aggressive brain tumor in adults

If you or someone you love has been diagnosed with a glioma, it’s important to talk with your care team about molecular testing. SurvivorNet’s AI‑powered tool, “My Health Questions,” can also help you better understand your diagnosis, explore treatment options, and prepare meaningful questions for upcoming appointments.

Questions To Ask Your Doctor

• Have I/can I undergo genetic testing for my tumor?
• What specific mutations will you be testing for in my tumor?
• Do I have any genetic mutation that would change the course of my treatment?
• Am I eligible to receive targeted therapy? What about immunotherapy?
• Is there a clinical trial that would be relevant for me?

Learn more about SurvivorNet's rigorous medical review process.

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