Repurposing Brigatinib to Treat NF2-Related Schwannomatosis

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Researchers have found that brigatinib may be effective in treating patients with NF2-related schwannomatosis, according to a recent study published by Plotkin et al in The New England Journal of Medicine. The findings revealed a potential new treatment option for the genetic syndrome.


Patients with NF2-related schwannomatosis—a rare and progressive condition—have tumors that develop on the covering of the brain or grow along the nerves in the brain, spinal cord, and/or other locations in the body.

Previous studies have shown that brigatinib may have tumor-suppressing properties in cell and animal models of NF2-related diseases. Brigatinib is currently approved by the U.S. Food and Drug Administration to treat lung cancer.

“The tumors of NF2-related schwannomatosis can cause a lot of problems, and there aren’t any approved treatments for these tumors yet,” explained lead study author Scott Plotkin, MD, PhD, Professor of Neurology at Harvard Medical School and Executive Director of the Pappas Center for Neuro-Oncology at Massachusetts General Hospital. “Progressive tumors can lead to deafness, weakness, immobility, and even death. We wanted to see if a drug called brigatinib could help patients,” he emphasized.

Study Methods and Results

In the recent phase II clinical trial, the researchers assigned 40 adult and adolescent patients with NF2-related schwannomatosis as well as progressive tumors—including vestibular schwannomas, nonvestibular schwannomas, meningiomas, and ependymomas—to receive oral brigatinib.

The researchers discovered that 10% of growing tumors and 23% of all tumors shrank in response to brigatinib. The tumors most impacted were meningiomas located in the brain and nonvestibular schwannomas that were not along the hearing nerve. Some patients reported improvements in hearing and pain after treatment.

The researchers noted that an important aspect of the study was that it was an “adaptive platform-basket” trial that provided an assessment of brigatinib’s activity across multiple NF2-related tumor types. The adaptive design screened for futility during enrollment and preferentially recruited patients with target tumors that were most likely to respond to treatment. In the first stage of the trial, 20 patients were enrolled, with a minimum of 2 patients per tumor basket. After the patients were treated for 6 months, an interim analysis was performed, and 20 additional patients with progressive tumors from the two most promising baskets were enrolled in the second stage of the trial.


“The platform-basket trial design allows rapid evaluation of investigational agents for genetic conditions with multiple manifestations,” detailed Dr. Plotkin. “In this study, brigatinib seemed to help with different types of tumors in [patients] with NF2-[related schwannomatosis],” he suggested.

The researchers plan to investigate the efficacy of other drugs using a similar strategy to determine whether drug combinations with brigatinib may further improve tumor responses in patients with the genetic syndrome.

“We are thrilled to see the promising results of brigatinib in treating NF2-related schwannomatosis, showcasing the power of collaborative partnerships in the fight against rare diseases,” underscored Annette Bakker, PhD, Chief Executive Officer of the Children’s Tumor Foundation. “This breakthrough highlights the importance of bringing together public institutions—including NCATS, private enterprises, and nonprofit organizations—to develop effective treatments that can significantly improve the lives of those affected by NF2-related schwannomatosis,” she concluded.

Disclosure: The research in this trial was supported by Takeda Pharmaceuticals, the Andrea Cahill Foundation, and the Children’s Tumor Foundation. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.