2 - A Prospective, Phase II Study of ¹⁷⁷Lu-Dotatate in Patients with Surgery- and Radiation-Refractory Meningioma: Results of the WHO Grade II/III Cohort

K. W. Merrell¹, D. R. Johnson², K. O. Steinert³, M. Ruff⁴, W. Breen¹, H. J. Gunn³, D. H. Lachance⁴, C. L. Goergen³, E. S. Yan¹, U. Sener⁴, S. Kizilbash⁵, J. H. Uhm⁴, P. D. Brown¹, N. N. Laack II¹, and G. B. Johnson²; ¹Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ²Mayo Clinic, Division of Nuclear Medicine, Rochester, MN, ³Mayo Clinic, Rochester, MN, ⁴Mayo Clinic, Department of Neurology, Rochester, MN, ⁵Mayo Clinic, Department of Medical Oncology, Rochester, MN

Purpose/Objective(s): Meningioma is the most frequently encountered brain tumor and typically managed with surgery and/or radiotherapy. However, recurrence rates for WHO grade II and III meningioma are reported as high as 40-80%, respectively. With each recurrence, safe and effective salvage options are quickly exhausted, leading to significant morbidity and mortality. As nearly all meningiomas express somatostatin receptors, we evaluated the efficacy of lutetium-177 (¹⁷⁷Lu)–Dotatate for refractory meningioma. Materials/

Methods: This is a single-arm, phase II clinical trial conducted at a single, large academic center. Eligible patients included those with surgery- and radiation-refractory meningioma with measurable disease and = 15% growth over a 6-month period. ⁶⁸Ga-DOTATATE PET/MRI was performed and a Krenning score of = 2 was required. ¹⁷⁷Lu-Dotatate was delivered at a dose of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 administrations. MRI brain was performed prior to each administration. The primary endpoint was progression-free survival at 6 months (PFS-6). Exceeding the established RANO historical benchmark of 26% for PFS-6 signaled a promising therapy. Secondary endpoints include PFS, overall survival (OS), and rates of adverse events (AE) at least possibly related to the investigational agent. A separate WHO grade I cohort continues to enroll.
Results: From April 2020 to April 2023, 26 patients were screened and 20 met all eligibility requirements and were enrolled into the WHO grade II/III cohort. The median age was 66.8 years (range, 38.9-85.0) and 95% had WHO grade II meningioma. ECOG PS was 0, 1, and 2 in 55%, 35%, and 10% of patients, respectively. A total of 40% of patients had a history of seizures and 65% had a history of neurologic deficit related to the refractory tumor, though only 15% were receiving corticosteroids at the time of enrollment. A Krenning score of 2, 3 and 4 was observed in 45%, 45%, and 10% of patients, respectively. PFS-6 and median PFS was 77.8% (95% CI: 52-94) and 10.7 months, respectively. Median survival was not reached. 1-year OS was 88.5% (95% CI: 47-96). There was no grade 4 or 5 AE attributable to treatment. A total of 10 patients experienced grade 3 hematologic AE with two patients experiencing grade 3 hepatitis (n=1) and grade 3 seizure (n=1), at least possibly attributed to treatment. 5 patients did not complete all 4 administrations due to possible treatment related AE (n=2), tumor progression (n=2), and other comorbidities (n=1).
Conclusion: This phase II clinical trial met the primary endpoint of PFS-6 and represents a significant milestone for surgery- and radiation-refractory meningioma as one of the first prospectively evaluated systemic agents to yield substantial clinical efficacy, surpassing established clinical benchmarks with reasonable safety profile. ¹⁷⁷Lu-Dotatate PFS appears as a safe and rational therapeutic choice with broad eligibility for the patient population under study, particularly as alternative therapy options are limited.