An Important Milestone for Treatment-Resistant Meningioma with 177Lu-Dotatate

Meningioma is a cancer that begins between the skull and brain or between the spine and spinal cord; in other words, it is cancer of the membrane surrounding the central nervous system. Brain tumors are included among central nervous system cancers, and meningioma is the most common type. It is generally treated with surgery or radiotherapy. Some patients, however, experience disease progression despite these standard treatments. This is called “refractory (treatment-resistant) meningioma”, and treatment options for these patients are very limited.

Clinical studies of 177Lu-Dotatate, considered an important development in refractory meningioma treatment, are producing promising results in this patient group. In a phase 2 clinical study presented at the ASTRO Annual Meeting 2024, 177Lu-Dotatate achieved significant results in patients with refractory meningioma, marking a new treatment milestone.

What Is 177Lu-Dotatate?

177Lu-Dotatate is a radionuclide therapy targeting somatostatin receptors. Approved particularly for neuroendocrine tumors, it is also considered a potential option for patients with refractory meningioma. A particular subtype of meningioma cells highly expresses somatostatin receptors, providing the basis for the hypothesis that 177Lu-Dotatate (lutetium therapy) could be effective in these patients.

Somatostatin receptors are protein structures that bind to the hormone somatostatin and transmit its effects into the cell. Their functions generally include regulating hormone secretion, controlling cell growth, and regulating digestive system functions. They are expressed at high levels, particularly in neuroendocrine tumors and certain other tumors such as meningioma, making them important targets for therapy.

Details of the Lutetium Clinical Study in Meningioma: Key Data

The study presented by Dr. Kenneth Merrell of Mayo Clinic examined 20 patients with stage II and III refractory meningioma. They had previously received surgery and/or radiotherapy, but their disease had not responded. Of the patients, 95% had stage II meningioma, 65% had neurological deficits, and 60% had a history of seizures. Participants received 4 cycles of 177Lu-Dotatate at a dose of 7.4 GBq (200 mCi).

Summary of Results:

• 6-Month Progression-Free Survival (PFS) Rate: 77.8%
• 2-Year PFS Rate: 26.7%
• Median PFS: 11.5 months
• Median Overall Survival (OS): 27.8 months
• 1-Year Overall OS Rate: 88.9%
• 2-Year OS Rate: 63.8%

These results show a significant improvement over the previously established historical progression-free survival rate of 26% . The study's primary endpoint, the 6-month PFS rate, exceeded the historical reference threshold of 26%, reaching 77.8%, leading to the conclusion that the treatment could be a “promising” option. Median overall survival of 27.8 months is also considered an important achievement for the treated patients.

Adverse Effects and Safety Profile

Common mild to moderate adverse effects included fatigue (90%), decreased lymphocyte count (65%), anemia (50%), decreased platelet count (50%), and nausea (50%). Severe treatment-related adverse effects were limited. No grade 4 or 5 adverse effects were reported; grade 3 events included decreased lymphocyte count (50%), anemia (5%), seizures (5%), and liver failure (5%). Given the limited alternative treatments available for refractory meningioma, this safety profile suggests that the treatment is acceptable.

Conclusion: A Step Toward Future Treatment Strategies

For many years, treatment options for refractory meningioma have remained limited. This study of 177Lu-Dotatate offers promising results and points to a development that could reshape future treatment strategies. The clinical findings indicate a need for larger studies to monitor treatment progress. Whether 177Lu-Dotatate might also be effective in tumors other than meningioma may be worth investigating.

In light of these developments, broader use of 177Lu-Dotatate in refractory meningioma and monitoring of long-term outcomes stand out as an important treatment strategy for this patient group.