A phase 3 randomised study of 177Lu-edotreotide or everolimus in patients with advanced neuroendocrine tumors of lung or thymic origin (LEVEL, GETNE-T2217)

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Introduction: Retrospective data for peptide receptor radionuclide therapy (PRRT) have demonstrated promising activity in somatostatin receptor (SSTR)-positive lung neuroendocrine tumors (NETs).

Aim(s): This study aims to compare the efficacy, safety, and patient-reported outcomes of 177Lu-edotreotide versus the standard of care everolimus in patients (pts) with advanced lung and thymic NET.

Materials and methods: The LEVEL trial is a randomized, open-label, phase 3 international (France, Italy and, Spain) trial of 177Lu-edotreotide versus everolimus in pts with progressive, advanced, and well/moderately differentiated NETs of lung (typical/atypical) or thymic origin. Pts could be treatment naïve or have progressed (PD) on somatostatin analogues or ≤2 additional systemic treatments. Prior PRRT or mTOR inhibitors are not permitted. Eligible pts are randomly assigned 3:2 to 6 cycles of 177Lu-edotreotide (total dose 7.5±0.7 GBq / cycle) or to oral everolimus 10 mg once daily until PD or unacceptable toxicity. 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. Secondary endpoints include overall response rate, overall survival, safety, and quality of life (EORTC QLQ-C30). The expected sample size is 120 pts using a two-sided Lan-DeMets with O’Brian-Fleming-like boundaries test to demonstrate statistical significant risk reduction of 46.4% (HR= 0.536) in PFS between arms (α=0.05, β=0.2).

Conference:

Presenting Author:

Authors: García-Álvarez A, Garcia-Carbonero R, Anido U, Jimenez-Fonseca P, Del Olmo-García M,

Keywords: Lung NET, Peptide receptor radionuclide therapy,