A radiopharmaceutical therapy has demonstrated early efficacy in patients with difficult-to-treat meningioma, according to new findings presented by Merrell et al at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 2) and simultaneously published in the International Journal of Radiation Oncology • Biology • Physics.
Background
Meningiomas are the most common types of primary brain tumors. Although they typically do not metastasize to other parts of the body, they can grow uncontrollably and cause disabling and potentially fatal compression of the nerves and brain.
Standard treatment for meningiomas is either surgical removal or external-beam radiation therapy when tumors grow in areas where surgery is too dangerous, including close to the brain stem or spinal cord. However, among the patients with refractory meningioma, the tumors tend to behave more aggressively, and retreatment is difficult because radiation and surgery cannot be repeated frequently without greater risks.
“There is no standard of care or proven option for managing refractory meningioma. Many of these patients continue to experience aggressive tumor growth and significant related complications, and ultimately the [disease] may prove fatal. It is a very challenging prognosis to manage, and in many cases, we are left with only supportive measures,” explained lead study author Kenneth W. Merrell, MD, a radiation oncologist at the Mayo Clinic Alix School of Medicine.
Theranostics—an approach that combines therapy with diagnostics for personalized internal delivery of radiation treatment—leverages radiopharmaceuticals to identify cancer cells in the body and attack them with precise doses of radiation without harming the surrounding healthy tissue. This dual-pronged approach can offer patients a more tailored and potentially more effective treatment option.
While still an emerging treatment modality, radiopharmaceuticals are commonly used to treat thyroid cancer, metastatic cancer such as bone metastases from prostate cancer, and other types of tumors. The radiopharmaceutical therapy lutetium (Lu)-177–dotatate is a U.S. Food and Drug Administration–approved treatment that has previously been shown to successfully extend progression-free survival in patients with neuroendocrine tumors, which share biological similarities with meningiomas.
Study Methods and Results
In the new, single-arm phase II clinical trial, researchers assessed whether patients with refractory meningiomas could benefit from theranostics. During a 3-year period beginning in April 2020, they enrolled patients with a median age of 67 years who had meningiomas that had grown at a rate of 15% or more over a 6-month period—including 20 patients with World Health Organization grade 2 or 3 disease. Nearly all of the patients (95%) involved in the study had grade 2 meningiomas. The patients were then assigned to receive four infusions of Lu-177–dotatate spaced 8 weeks apart.
The researchers discovered that 6 months following treatment, 78% of the patients had not experienced further tumor progression, far exceeding the benchmark progression-free survival rate of 26% established by prior research. The median time before cancer progression was 11.5 months.
“Nearly 80% of patients in our study were progression-free after 6 months. This rate greatly surpassed the benchmark from prior research, suggesting that radiopharmaceuticals are a promising therapeutic agent for these patients,” Dr. Merrell indicated.
Additionally, after a follow-up of 1 year, the overall survival rate was 88.9%. None of the patients experienced life-threatening side effects, whereas 10 of them had severely low blood counts, 1 of them had grade 3 hepatitis, and 1 of them had a grade 3 seizure that was potentially related to treatment. Five of the patients did not complete treatment as a result of tumor progression (n = 2), adverse events that were potentially related to treatment (n = 2), or other comorbidities (n = 1).
Conclusions
“There have been many attempts at testing a variety of chemotherapies and other systemic agents [in] these patients. And others have looked at this option for therapy, but no one had completed a prospective trial for this patient population before ours,” noted senior study author Geoffrey B. Johnson, MD, PhD, a nuclear medicine physician at the Mayo Clinic. “With advanced [positron-emission tomography] imaging, the theranostic approach to treatment helps us to select those patients most likely to benefit from molecularly targeted radiation directly to their tumor cells,” he continued.
“We’ve found a therapy with a meaningful signal for effectiveness and safety [in patients] with refractory meningioma, a condition with no standard treatment options,” said Dr. Merrell. “Most patients tolerated the treatment well. It appears that [Lu-177–dotatate] is a safe and rational therapeutic choice with broad eligibility [in] patients with aggressively growing meningiomas, particularly as alternative therapy options are limited. As there is no current standard of care for these patients, our findings establish a new benchmark and may influence the treatment options available,” he concluded.
Disclosure: The research in this study was supported by Novartis. For full disclosures of the study authors, visit astro2024.eventscribe.net and redjournal.org.
