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- Eigler, Christopher, et al.
(författare)
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Radiolabeled Somatostatin Receptor Antagonist Versus Agonist for Peptide Receptor Radionuclide Therapy in Patients with Therapy-Resistant Meningioma: PROMENADE Phase 0 Study
- 2024
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Ingår i: JOURNAL OF NUCLEAR MEDICINE. - 0161-5505 .- 1535-5667. ; 65:4, s. 573-579
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Tidskriftsartikel (refereegranskat)abstract
- Our primary aim was to compare the therapeutic index (tumor-to- bone marrow and tumor -to -kidney absorbed -dose ratios) of the new radiolabeled somatostatin receptor antagonist [ 177 Lu]Lu-DOTA-JR11 with the established radiolabeled somatostatin receptor agonist [ 177 Lu]Lu-DOTATOC in the same patients with progressive, standard therapy -refractory meningioma. Methods: In this prospective, singlecenter, open -label phase 0 study (NCT04997317), 6 consecutive patients were included: 3 men and 3 women (mean age, 63.5 y). Patients received 6.9-7.3 GBq (standard injected radioactivity) of [ 177 Lu]Lu-DOTATOC followed by 3.3-4.9 GBq (2 GBq/m 2 3 body surface area) of [ 177 Lu]Lu-DOTA-JR11 at an interval of 10 6 1 wk. In total, 1 [ 177 Lu]Lu-DOTATOC and 2-3 [ 177 Lu]Lu-DOTA-JR11 treatment cycles were performed. Quantitative SPECT/CT was done at approximately 24, 48, and 168 h after injection of both radiopharmaceuticals to calculate meningioma and organ absorbed doses as well as tumor -to -organ absorbed -dose ratios (3 -dimensional segmentation approach for meningioma, kidneys, liver, bone marrow, and spleen). Results: The median of the meningioma absorbed dose of 1 treatment cycle was 3.4 Gy (range, 0.8-10.2 Gy) for [ 177 Lu]Lu-DOTATOC and 11.5 Gy (range, 4.7-22.7 Gy) for [ 177 Lu]Lu-DOTA-JR11. The median bone marrow and kidney absorbed doses after 1 treatment cycle were 0.11 Gy (range, 0.05-0.17 Gy) and 2.7 Gy (range, 1.3- 5.3 Gy) for [ 177 Lu]Lu-DOTATOC and 0.29 Gy (range, 0.16-0.39 Gy) and 3.3 Gy (range, 1.6-5.9 Gy) for [ 177 Lu]Lu-DOTA-JR11, resulting in a 1.4 (range, 0.9-1.9) times higher median tumor-to-bone marrow absorbed -dose ratio and a 2.9 (range, 2.0-4.8) times higher median tumor -to -kidney absorbed -dose ratio with [ 177 Lu]Lu-DOTA-JR11. According to the Common Terminology Criteria for Adverse Events version 5.0, 2 patients developed reversible grade 2 lymphopenia after 1 cycle of [ 177 Lu]Lu-DOTATOC. Afterward, 2 patients developed reversible grade 3 lymphopenia and 1 patient developed reversible grade 3 lymphopenia and neutropenia after 2-3 cycles of [ 177 Lu]Lu- DOTA-JR11. No grade 4 or 5 adverse events were observed at 15 mo or more after the start of therapy. The disease control rate was 83% (95% CI, 53%-100%) at 12 mo or more after inclusion. Conclusion: Treatment with 1 cycle of [ 177 Lu]Lu-DOTA-JR11 showed 2.2-5.7 times higher meningioma absorbed doses and a favorable therapeutic index compared with [ 177 Lu]Lu-DOTATOC after injection of 1.4-2.1 times lower activities. The first efficacy results demonstrated a high disease control rate with an acceptable safety profile in the standard therapy for refractory meningioma patients. Therefore, larger studies with [ 177 Lu]Lu-DOTA-JR11 are warranted in meningioma patients.
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