Repurposed Drug Shrinks NF2-related Schwannomatosis Tumors
Article Summary
- Researchers have evidence that the approved lung cancer drug, brigatinib, may shrink tumors associated with neurofibromatosis type 2 (NF2)-related schwannomatosis.
- Dr. Christine Dinh collaborated in a study of patients with NF2-related schwannomatosis who took brigatinib for 36 months.
- The study confirmed 10% of growing tumors and 23% of all tumors shrank and one-third of patients experienced improvement in hearing and pain.
Researchers from major centers around the world that treat and study neurofibromatosis type 2 (NF2)-related schwannomatosis, including the University of Miami Miller School of Medicine, have promising evidence that the approved lung cancer drug, brigatinib, may shrink tumors associated with this progressive genetic syndrome.
The research team’s phase 2 study findings were published today in the New England Journal of Medicine (NEJM).
“The importance of this and similar studies cannot be overstated,” said Fred F. Telischi, M.D., professor of otolaryngology, neurological surgery and biomedical engineering and chairman of the Miller School’s Department of Otolaryngology—Head and Neck Surgery. “New and repurposed drugs found to have beneficial effect in preclinical studies must find an expeditious route to human clinical trials. This paper describes just such an innovative approach in a multi-institutional effort to find effective medications for a particularly difficult-to-treat and frequently devastating condition.”
A Difficult Disease to Treat
Patients with NF2-related schwannomatosis develop multiple tumors types, including vestibular schwannomas, non-vestibular schwannomas, meningiomas and ependymomas.
Many patients experience hearing loss, deafness, weakness and loss of mobility. Some even die, said study author Christine Dinh, M.D., associate professor of clinical otolaryngology and director of the Neurofibromatosis Type 2 and Vestibular Schwannoma Research Laboratory at the Miller School.
There are no approved treatments for NF2-related schwannomatosis. Doctors and surgeons manage progressive schwannomas meningiomas, and ependymomas associated with the syndrome with surgery, radiation or off-label chemotherapy.
Since these patients have multiple tumors throughout the nervous system, some treatments can cause neurological injury and reduced quality of life.
Potential Brigatinib Treatment Benefits
Dr. Dinh collaborated with the study’s lead author, Scott Plotkin, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School, as well as experts from New York University, Johns Hopkins University, Mayo Clinic and UCLA. They studied 40 adult and adolescent patients with NF2-related schwannomatosis whose tumors were progressing. Patients took brigatinib daily and were followed for about 36 months.
The research team found that in response to the small molecule brigatinib, 10% of growing tumors and 23% of all tumors in those studied shrank. Up to one-third of patients experienced objective improvement in hearing and reductions in pain.
Meningiomas in the brain and non-vestibular schwannomas were most likely to respond to the drug.
“Brigatinib is a well-tolerated oral medication,” Dr. Dinh said. “Undoubtedly, this clinical trial will make an important footprint in the field of NF2 research and establishes a new framework that allows us to speed scientific discovery and NF2 treatment.”
Researchers used an innovative phase 2 basket trial design, which was important given the multiple tumor types and the urgency for new treatment options.
“The platform-basket trial design allows us to evaluate more than one chemotherapy in NF2 patients by performing multi-arm, phase 2 clinical trials. It is also unique because we can evaluate the effect of each chemotherapy on multiple tumor types that occur in NF2,” Dr. Dinh said. “The clinical trial employs an adaptive study design that even allows us to drop treatments after interim analysis in the first stage of the trial, if the treatment is not effective at shrinking tumors or is not well tolerated by patients.”
Springboard for Future Research
Innovative research like this requires support and collaboration, according to Dr. Dinh.
“The Miller School and Sylvester Comprehensive Cancer Center’s support has allowed us to develop a translational and clinical research platform to study and advance patient care toward precision and personalized medicine in NF2 and in the treatment of vestibular schwannoma tumors that cause hearing loss,” Dr. Dinh said. “We are grateful that our collaborative research with Cristina Fernandez-Valle, Ph.D., at University of Central Florida, and other colleagues in this NEJM study, along with the Children’s Tumor Foundation, has allowed us to contribute toward this important endeavor of bringing new and effective therapies from bench to bedside.”
The trial brought together a diverse, expert Miller School group, including pediatric hematologist-oncologist Aditi Dhir, M.D., senior audiologist Sandra Velandia, Au.D., lead neuro-radiologist Rita Bhatia, M.D., and other multidisciplinary collaborators.
The goal is to continue the progress from this work to identify new therapies that may preserve hearing, shrink tumors and improve quality of life in NF2 patients.
“Through our collaborative efforts, we will work diligently toward finding a cure for NF2,” Dr. Dinh said.
The Miller School has access to diverse populations of patients, including the southeastern U.S., the Caribbean and Latin America. It was the first institution in Florida to introduce the Auditory Brainstem Implant program that uses signals to bring back sound for people without auditory nerve function.
The Children’s Tumor Foundation connects NF2 researchers to share new discoveries and work together with the Miller School to advance new therapies from bench to bedside for NF2 patients.
“Annette Bakker and the Children’s Hearing Foundation have really helped facilitate support from federal, private and nonprofit organizations to carry out this NF2 clinical trial,” Dr. Dinh said.
Tags: Dr. Christine Dinh, Dr. Fred Telischi, INTUITT-NF2, otolaryngology, Schwann cells