Lutetium [Lu-177] oxodotreotide 7,400MBq/20.5-25ml solution for infusion vials

BackgroundDrug interactions with diagnostic radiopharmaceuticals are well recognized, as they can modify biodistribution and lead to false or misleading diagnostic results. However, little is known about such interactions in the field of therapeutic radiopharmaceuticals, despite their rapid expansion-particularly with targeted radionuclide therapies such as Radioligand Therapy (RLT). This review aims, for the first time, to systematically compile and analyze available data on drug interactions involving therapeutic radiopharmaceuticals, in order to support safer and more effective patient care.Main bodyEighty-three articles investigating drug interactions with [177Lu]Lu-oxodotreotide (Lutathera®), [177Lu]Lu-vipivotide tetraxetan (Pluvicto®), [131I]INa, [131I]I-meta-iodobenzylguanidine ([131I]I-MIBG), [223Ra]RaCl2 (Xofigo®), [90Y]Y-ibritumomab tiuxetan (Zevalin®) or [153Sm]Sm-lexidronam pentasodium (Quadramet®) were included. These studies reported 133 drug interactions, 69% of which were not mentioned in the corresponding summaries of product characteristics. Interactions could be beneficial (e.g., reducing renal toxicity) or harmful (e.g., decreasing therapeutic efficacy or potentiating toxicity). Three interactions involved complementary and alternative medicines (quercetin, Ginkgo biloba and ouabain). Overall, the evidence level for reported interactions was low: 88% were classified as level 3 or 4 according to the Centre for Evidence-Based Medicine (CEBM) scale.ConclusionDrug interactions with therapeutic radiopharmaceuticals remain underreported, yet they may have significant clinical consequences. Clinical radiopharmacy plays a key role in detecting and preventing these interactions. Radiopharmacists, through their expertise, can identify potential interactions, influence therapeutic decisions, and positively impact patient management. Their involvement throughout the care pathway is essential to ensure the safe and effective use of these innovative therapies. Nuclear medicine physicians should also be aware that such interactions can alter biodistribution, compromise therapeutic efficacy, and increase the risk of adverse effects.

Abstract licence: CC BY-NC-ND

BackgroundEverolimus is the only approved therapy for patients with advanced neuroendocrine tumors (NET) of lung and thymus and new treatment options are urgently needed. Expression of somatostatin receptor 2 (SSTR2) is frequently seen in functional imaging in lung-NETs opening the opportunity to treat SSTR2 positive patients with radioligand therapies (RLT). Retrospective data suggest a potential meaningful benefit of RLT directed to SSTR2 in lung-NET patients.MethodsThe LEVEL trial is a randomized, open-label, phase III international trial of 177Lu-edotreotide versus everolimus in patients with progressive, locally advanced or metastatic, and well/moderately differentiated NETs of lung (typical/atypical) or thymic origin. Patients could be treatment-naïve or have progressed (PD) on somatostatin analogues or ≤ 2 additional systemic treatments. Prior RLT or mTOR inhibitors are not permitted. Eligible patients are randomly assigned 3:2 to 6 cycles of 177Lu-edotreotide (total administered activity 7.5 ± 0.7 GBq / cycle) or to oral everolimus 10 mg once daily until PD or unacceptable toxicity. Only patients with positivity in somatostatin receptor imaging will be included. CT or MRI scans are performed every 12 weeks until PD. Blood samples are analyzed at baseline, at 1st tumor assessment, and at PD for pharmacodynamic endpoints. Archival tumor tissue samples will be analyzed for ancillary studies. The primary endpoint is progression-free survival (PFS) according to RECIST v1.1 based on local investigator assessment. Secondary endpoints include overall survival, overall response rate, safety, and quality of life (EORTC QLQ-C30). The expected sample size is 120 patients to demonstrate statistical significant risk reduction of 46.4% (HR = 0.536) in PFS with the experimental treatment using an overall 5% two-sided alpha error with 80% power. An interim PFS analysis was included using the Lan-DeMets with O'Brian-Fleming-like boundaries.DiscussionThe LEVEL trial will investigate if 177Lu-edotreotide has the potential to be incorporated as a standard treatment option for patients with NETs from the lung and Thymus.Trial registrationEU CT: 2022-502154-13-00 / www.Clinicaltrialsgov : NCT05918302 (June 23rd, 2023).

Abstract licence: CC BY-NC-ND