Year Book of Dermatology

Abstract

The objective of this study was to assess the safety, dosimetry, and efficacy of the ¹⁷⁷Lu-labeled somatostatin receptor (SSTR) antagonist DOTA-p-Cl-Phe-cyclo (D-Cys-Tyr-D-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH2 (¹⁷⁷Lu-DOTA-LM3) in patients with metastatic neuroendocrine neoplasms (NENs). <b>Methods:</b> Fifty-one patients (age 27–76, mean 51.6±13.9 years) with metastatic NENs underwent peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTA-LM3 between August 2017 and December 2019. The median administered activity per cycle was 6.1±0.88 GBq (range 2.8–7.4 GBq). ⁶⁸Ga-NODAGA-LM3 PET/CT was used for patient selection and follow-up after ¹⁷⁷Lu-DOTA-LM3 PRRT. Morphologic and molecular responses were evaluated in accordance with RECIST 1.1 and European Organization for Research and Treatment of Cancer (EORTC) criteria. Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dosimetry was performed in 11 patients and compared with the SSTR agonist ¹⁷⁷Lu-DOTATOC in 247 patients undergoing PRRT on the same dosimetry protocol. <b>Results:</b> Higher uptake and a longer effective half-life of ¹⁷⁷Lu-DOTA-LM3 was found for whole-body as well as kidneys, spleen, and metastases, resulting in higher mean absorbed organ and tumor doses as compared to the agonist ¹⁷⁷Lu-DOTA-TOC. All patients tolerated therapy without any serious acute adverse effects. Mild nausea without vomiting was observed in 5 (9.8%) patients; no other symptoms were reported. The most severe delayed adverse event was CTC-3 thrombocytopenia in 3 (5.9%) patients. Neither CTC-4 thrombocytopenia nor CTC-3-4 anemia or leukopenia was observed after treatment. No significant decline in renal function was observed, nor was hepatotoxicity. According to RECIST 1.1, disease control could be reached in 40 patients (disease control rate, 85.1%) of 47 patients monitored after ¹⁷⁷Lu-DOTA-LM3 PRRT, with a partial response in 17 (36.2%) and stable disease in 23 (48.9%), whereas 7 (14.9%) patients had progressive disease, and by EORTC criteria, complete remission in 2 (4.3%), partial remission in 21 (44.7%), stable disease in 18 (38.3%), and progressive disease in 6 (12.8%) patients. <b>Conclusion:</b> “Antagonist PRRT” with ¹⁷⁷Lu-DOTA-LM3 could be administered without severe adverse effects and was well tolerated by the majority of patients, with thrombocytopenia occurring only in a few patients. No other severe adverse effects were observed, particularly no nephrotoxicity. The SSTR antagonist ¹⁷⁷Lu-DOTA-LM3 appears to be very promising for PRRT, provides favorable biodistribution and higher tumor radiation doses than SSTR agonists, and was very effective in treating advanced metastatic NENs, especially in patients with low or no SSTR agonist binding, even achieving complete remission in some patients.