An Experimental Medicine May Slow Pediatric Brain Cancers

According to a clinical trial published in Nature Medicine, the medicine Tovorafenib may slow or decrease the growth of some pediatric brain cancers.

According to the National Institutes of Health, pediatric low-grade gliomas account for around 30% of all pediatric brain cancers, with mutations in the BRAF gene being the most prevalent genetic drivers.

Some juvenile low-grade gliomas can be treated surgically, however for many children, the tumor’s location renders the malignancy inoperable. The American Brain Tumor Association reports that children with inoperable tumors frequently require numerous rounds of chemotherapy or radiation throughout their first few years of life.

More than 100 young adults aged six months to 25 years with low-grade brain tumors caused by a BRAF mutation received a weekly dosage of Tovorafenib, which inhibits production of the related RAF gene. The novel medicine does not produce paradoxical activation of the BRAF fusions as shown with the first generation of RAF inhibitors, a discovery first described by Waanders and her team in a 2013 research published.

According to the study, 67 percent of trial participants responded to the medicine after a median of three months. Tumor volume was significantly decreased in 37 percent of participants, while tumor development was stopped in 26 percent.

The study’s findings suggest that Tovorafenib may be a viable treatment option for many patients with low-grade pediatric gliomas who have not responded to other treatments, according to Angela Waanders, MD, MPH, associate professor of Pediatrics in the Division of Hematology, Oncology, and Stem Cell Transplantation and study co-author.

“Beyond response rate, what’s important to note is that this is a once-a-week drug, which is different than other similar inhibitors on the market,” said Waanders, who also works at Northwestern University’s Robert H. Lurie Comprehensive Cancer Center. “Other inhibitors often need to be taken on an empty stomach, once or twice a day, which means nothing to eat or drink a few hours before taking the drug for pediatric patients, but Tovorafenib doesn’t require that. From a quality-of-life standpoint, that makes Tovorafenib an attractive option.”

The study found that the most common side effects were hair color changes, increased creatine phosphokinase, and anemia.

After the initial Phase 2 trial concluded, the business offered an enhanced access program, making it easier for researchers at the Ann & Robert H Lurie Children’s Hospital of Chicago to make the medicine available to out-of-state patients, according to Waanders.

Waanders said, “Equity of access is really important to us, and we were able to provide this drug to patients in the Chicagoland area as well as patients residing in nearby states.”

Waanders stated that more trials are planned or have already begun that will combine this medication with other therapies, such as immunotherapy for BRAF mutant juvenile brain cancers.

Following the trial, Tovorafenib is pending FDA approval.

Day One Biopharmaceuticals supported the study. Waanders is on the company’s scientific advisory board for pediatric low-grade gliomas.

More information: Lindsay B. Kilburn et al, The type II RAF inhibitor Tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial, Nature Medicine (2023). DOI: 10.1038/s41591-023-02668-y

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