2026-04-13T03:59:57Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/130922025-05-16T03:39:38Zcom_2072_378070com_2072_378040col_2072_378092

2025-05-16T03:39:37Z urn:hdl:11351/13092 A Randomized clinical trial evaluating the impact on survival and quality of life of 177Lutetium[Lu]-edotreotide versus everolimus in patients with neuroendocrine tumors of the lung and thymus: the LEVEL study (GETNE T-2217) Pubul Núñez, Virginia Anido Herranz, Urbano Walter, Thomas Hernando, Jorge Garcia-Alvarez, Alejandro Capdevila Castillon, Jaume Molina-Cerrillo, Javier Alonso-Gordoa, Teresa Garcia-Burillo, Amparo Villacampa Javierre, Guillermo Avaluació de resultats (Assistència sanitària) Pulmons - Càncer - Tractament Tumors neuroendocrins - Tractament Tim - Càncer - Tractament Medicaments antineoplàstics - Ús terapèutic CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents Other subheadings::Other subheadings::/therapeutic use ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors Other subheadings::Other subheadings::Other subheadings::/drug therapy DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Thymus Neoplasms DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos Otros calificadores::Otros calificadores::/uso terapéutico TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del timo ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares Everolimus; Neuroendocrine tumors; Targeted radioligand therapy Everolimus; Tumors neuroendocrins; Teràpia amb radiolligands dirigits Everolimus; Tumores neuroendocrinos; Terapia con radioligandos dirigidos Background Everolimus 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. Methods The 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. Discussion The 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 Registration EU CT: 2022–502154-13–00 / www.clinicaltrials.gov: NCT05918302 (June 23rd, 2023). This work was sponsored by the Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE) with the collaboration of ITM Oncologics GmbH. 2025-05-16T03:39:37Z 2025-05-16T03:39:37Z 2025-05-15T08:23:43Z 2025-05-15T08:23:43Z 2025-04-04 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/13092 BMC Cancer;25 https://doi.org/10.1186/s12885-025-13941-3 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess BMC Scientia