177Lu-Dotatate Is a Viable Treatment in Meningioma

TREATMENT WITH LUTETIUM 177 dotatate (177Lu-dotatate; Lutathera) showed activity and met the progression-free survival (PFS) end point in patients with surgery- or radiation-refractory grade 2/3 meningioma, according to data from a prospective phase 2 trial presented during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting in Washington, DC.¹

The median PFS was 11.5 months, and the 2-year PFS rate was 26.7% (95% CI, 12%-58%). The median overall survival (OS) was 27.8 months. The 1-year OS rate was 88.9% (95% CI, 76%-100%), and at 2 years, it was 63.8% (95% CI, 44%-92%). The best response achieved was stable disease. “Considering limited alternative therapies, our results support 177Lu-dotatate as a rational therapeutic choice,” Kenneth W. Merrell, MD, a radiation oncologist at the Mayo Clinic Alix School of Medicine in Rochester, Minnesota, said during the presentation.

Meningioma is the most common brain tumor, with 25,000 cases or more annually across the United States, Merrell explained. For World Health Organization (WHO) grades 2 and 3, the recurrence risk is 40% to 80% and the mortality risk is 2 to 3 times higher compared with grade 1. At the time of recurrence, the tumor behavior can often be aggressive. Currently, there are limited options post surgery and radiation, and systemic therapy remains off-label, with no proven efficacy.

Merrell stated that somatostatin receptor 2 (SSTR2) is expressed in 80% to 100% of meningiomas across all grades. Peptide receptor radionuclide therapy uses a peptide that can be linked to a radionuclide, allowing 177Lu-dotatate to bind with high affinity to SSTR2. Additionally, 177Lu-dotatate can be used for specific and targeted radiation for refractory meningioma and has the potential for broad applicability.²

Findings from the Simon 2-stage–designed trial presented at the ASTRO meeting focused on patients in the study cohort with WHO grades 2 and 3. Patients were registered for the trial and received gallium dotatate PET/MRI followed by 4 cycles of 177Lu-dotatate at 8-week intervals. A single-photon emission CT/CT dosimetry occurred after the first cycle of 177Lu- dotatate, which was between 23 and 168 hours post infusion. Active monitoring was done annually.

Twenty patients were enrolled, with a median age of 66.8 years. Thirty-five percent of patients were female, and 55% had an ECOG performance status of 0. A total of 65% of patients had a neurological deficit, 60% had a seizure history, and 15% had received a corticosteroid.

Tumor characteristics included 95% of patients having a WHO grade of 2, 55% having a Krenning score of 2 or more, and the largest tumor with a 3.5 SD within a 1.8-cm to 7.5-cm range. All patients previously underwent surgery. Additionally, the median number of prior courses of radiotherapy was 2 and 15% of patients had prior chemotherapy.

The clinical outcomes benchmark was the Response Assessment in Neuro-Oncology, which was the systematic review of 47 studies to establish the 6-month PFS (PFS-6) benchmarks for future trial designs. For WHO grades 2 and 3, the PFS-6 rate at benchmark was 26%. Seventy percent of patients received 4 infusions. For those with 4 or more cycles, 10% had adverse events (AEs), 10% had other medical problems, and 10% had progression. There were no AEs that were higher than grade 3 and attributed to 177Lu-dotatate. The rate of grade 3 nonhematologic AEs was 10%.

Merrell noted that based on these results, 177Lu-dotatate was well tolerated in this population. “[177Lu-dotatate] demonstrated clinically meaningful outcomes across a broad patient population, marking a significant milestone for refractory meningioma,” Merrell concluded.

REFERENCES:

1. Merrell KW, Johnson DR, Steinert KO, et al. A prospective phase II study of 177Lu-dotatate in patients with surgery- and radiation-refractory meningioma: results of the WHO grade II/III cohort. Abstract presented at: 2024 American Society for Radiation Oncology Annual Meeting; September 29-October 2, 2024; Washington, DC. Abstract 2.

2. Strosberg J, El-Haddad G, Wolin E, et al; NETTER-1 Trial Investigators. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. doi:10.1056/NEJMoa1607427