Volumetric MRI Tracks MEK Inhibitor Response in NF1 Tumors
Adults taking mirdametinib reached their smallest tumor size in about 15 months, while tumor shrinkage is measured on volumetric MRI scans about every six months in clinical trials, everydayhealth.com reported.
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Key Clinical Takeaways:
- Volumetric MRI tracks three-dimensional tumor size, requiring shrinkage of at least 20 percent to qualify as responsive in trials.
- Pain can start to improve as early as two months, and nearly 60 percent of adults with significant pain had meaningfully less pain within about four months.
- MEK inhibitors require long-term management, as tumors can grow back if the medication is stopped.
Tumor volume serves as a radiological benchmark for assessing whether a MEK inhibitor is working in patients with neurofibromatosis type 1, according to everydayhealth.com. Plexiform neurofibromas are measured with volumetric MRI to calculate full three-dimensional size, where a reduction of at least 20 percent was considered responsive when the change held up on a second scan two to six months later, everydayhealth.com reported.
Radiological Evaluation Timelines
Because tumor reduction takes several months to begin, conducting scans roughly twice a year represents an appropriate schedule, as noted to everydayhealth.com by Dr. Rebecca Brown, PhD, an associate professor of neurology at the University of Alabama at Birmingham Heersink School of Medicine in Birmingham. “If we scan too early and don’t see a change yet, patients can get discouraged,” Brown told everydayhealth.com.
Half of the people whose tumors responded in the adult selumetinib trial saw that response within about four months, while the mirdametinib trial took about eight months to reach that halfway point, everydayhealth.com reported. Adults in the mirdametinib trial typically required more than a year, or about 15 months, to reach their smallest tumor size, according to everydayhealth.com.
Functional Improvements Versus Tumor Shrinkage
“Pain can start to improve as early as two months after starting treatment. People may also function better before we see the tumor shrink, possibly because they're in less pain,” said Dr. Rebecca Brown, PhD, an associate professor of neurology at the University of Alabama at Birmingham Heersink School of Medicine in Birmingham, in an interview with everydayhealth.com.
Nearly 60 percent of adults in the mirdametinib trial who started out with significant pain experienced meaningfully less pain within about four months, everydayhealth.com reported.
Clinical trials rate worst tumor pain on a scale of 0 to 10 alongside quality-of-life questionnaires, everydayhealth.com reported. Outside major academic centers, those questionnaires are rarely part of everyday care, Brown told everydayhealth.com. “Those conversations are different for every patient,” Brown told everydayhealth.com, noting that quality of life may involve pain, strength, appearance, vision, swallowing, or clothing fit.
Comparative Trial Response Rates
| Medication Trial | Tumor Shrinkage of 20% or More | Median Time to Response |
|---|---|---|
| Mirdametinib (Adults) | About 2 out of 5 adults | About 8 months |
| Selumetinib (Adults) | 20 percent of adults | About 4 months |
About 2 out of 5 adults had their tumors shrink by at least 20 percent in the mirdametinib trial, compared with 20 percent of people in the main adult trial of selumetinib taking the drug versus 5 percent taking a placebo, everydayhealth.com reported.
“Both drugs worked better in the trials in children, where about 50 to 70 percent responded, but that may be because those children tended to have more severe or faster-growing tumors,” as Dr. Rebecca Brown, PhD, an associate professor of neurology at the University of Alabama at Birmingham Heersink School of Medicine in Birmingham, explained to everydayhealth.com.
Among participants showing a response to mirdametinib, over 60 percent experienced a reduction in tumor dimensions exceeding 50 percent, with select cases displaying decreases reaching up to 90 percent, per reporting by everydayhealth.com. Among people who responded to selumetinib, tumors typically shrank by about a third, while people whose tumors missed the 20 percent threshold still saw an average shrinkage of about 10 percent, everydayhealth.com reported.
Long-Term Treatment Management
People with NF1 are born with one copy of the NF1 gene that does not work, leaving a protein called MEK overactive and telling cells to grow and divide extra fast, Brown told everydayhealth.com. Both approved drugs are designed to block MEK, slowing tumor cell growth and cutting down surrounding material to shrink the tumor, according to everydayhealth.com.
Results tend to last while treatment continues, as all but one of the 24 adults whose tumors responded in the mirdametinib trial were still responding when results were analyzed, everydayhealth.com reported. “They only work while you’re taking them, and tumors have been reported to grow back after people stop,” Brown told everydayhealth.com.
Common practice involves staying on a MEK inhibitor for at least 18 months to two years, according to everydayhealth.com. Before utilizing anti-diarrheal pharmaceuticals like loperamide, Dr. Pierre Giglio, MD — an associate professor of neurology and director of neuro-oncology at the Ohio State University Wexner Medical Center in Columbus — recommended that patients first consult their medical providers.
Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice.