225Ac/177Lu-DOTATATE PRRT achieves 85.7% 6-month progression-free survival in advanced meningiomas

Progressive meningiomas pose a significant therapeutic challenge, with limited effective options for advanced or recurrent cases. Standard treatments like surgery or radiotherapy often fall short, leaving a critical gap for patients with inoperable or refractory disease. Peptide receptor radionuclide therapy (PRRT), which targets somatostatin receptors (SSTRs) highly expressed on these tumors, offers a promising strategy. This study explores the novel application of combined alpha-emitting [225Ac]Ac-DOTATATE and beta-emitting [177Lu]Lu-DOTATATE PRRT to address this unmet need in advanced meningiomas.

This pilot study enrolled 7 patients with inoperable or refractory meningiomas, all exhibiting high SSTR expression on [68Ga]Ga-DOTATATE PET/CT. Patients received a median of 4 PRRT cycles, utilizing a combination or sequential regimen of [225Ac]Ac-DOTATATE and [177Lu]Lu-DOTATATE. One patient was treated solely with 225Ac-DOTATATE. The primary endpoint was progression-free survival (PFS) at 6 months, assessed via Response Assessment in Neuro-Oncology (RANO) criteria. Secondary outcomes included overall survival (OS), clinical and imaging responses, and toxicity. Single-lesion dosimetry was performed for 1 patient.

The study reported a remarkable PFS-6 rate of 85.7% (95% CI: 42.1%-99.6%) among the 7 patients, indicating significant disease control at 6 months. Out of the 7 patients, 1 achieved complete clinical remission, 2 experienced partial remission, and 3 demonstrated stable disease, highlighting diverse but generally positive clinical responses. The median overall survival (OS) was 14 months (95% CI: 8-18 mo), suggesting a meaningful extension of life in this challenging patient population. At the lesion level (n = 25 lesions), semiquantitative SUVmax analysis revealed partial response in 4 lesions, stable disease in 19, and progressive disease in 2, underscoring heterogeneous tumor responses. The therapy was notably well-tolerated, with only mild, grade 1 hematological toxicities observed, suggesting a favorable safety profile. Single-lesion dosimetry in 1 patient calculated a tumor absorbed dose of 3.36 Gy/MBq for [225Ac]Ac-DOTATATE and 2.37 Gy/GBq for [177Lu]Lu-DOTATATE, providing initial insights into radiobiological effectiveness.