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The following is a summary of “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),” published in the April 2025 issue of BMC Cancer by Capdevila et al.

Neuroendocrine tumors (NETs) of the lung and thymus represent a rare and heterogeneous group of malignancies, often associated with limited therapeutic options once advanced disease develops. Everolimus currently remains the only approved systemic therapy for patients with advanced pulmonary or thymic NETs, highlighting a critical unmet need for novel, more effective treatments. A promising avenue involves targeting somatostatin receptor 2 (SSTR2), which is commonly overexpressed in lung-NETs and can be visualized through functional imaging modalities. This receptor profile offers a unique opportunity to employ radioligand therapies (RLT), such as ¹⁷⁷Lu-edotreotide, in appropriately selected patients. Retrospective studies have suggested favorable outcomes using SSTR2-directed RLT in patients with lung-NET, prompting the design of the LEVEL trial to rigorously assess this approach in a prospective setting. The LEVEL study is a randomized, open-label, international Phase III clinical trial comparing the efficacy and safety of ¹⁷⁷Lu-edotreotide versus oral everolimus in patients with well or moderately differentiated, progressive, locally advanced, or metastatic lung (typical or atypical) or thymic NETs. 

Eligible participants—confirmed to have SSTR2 positivity through somatostatin receptor imaging—are randomized in a 3:2 ratio to receive either 6 cycles of ¹⁷⁷Lu-edotreotide (administered at 7.5 ± 0.7 GBq per cycle) or daily everolimus (10 mg), continued until disease progression or unacceptable toxicity occurs. The trial permits inclusion of treatment-naïve patients or those with prior progression on somatostatin analogues and up to two prior systemic therapies, excluding previous exposure to RLT or mTOR inhibitors. Imaging evaluations using CT or MRI are performed at 12-week intervals, and blood samples are collected at baseline, during the first tumor assessment, and at progression to evaluate pharmacodynamic biomarkers. 

Additionally, archival tumor tissue will be used for ancillary exploratory analyses. The primary outcome measure is progression-free survival (PFS) as per RECIST v1.1, assessed by local investigators. Key secondary endpoints include overall survival, objective response rate, safety profile, and patient-reported quality of life using the EORTC QLQ-C30 instrument. The study aims to enroll 120 patients, with a statistical design powered to detect a 46.4% reduction in risk of disease progression (HR = 0.536) using a two-sided alpha of 5% and 80% power. An interim PFS analysis is planned based on the Lan-DeMets spending function with O’Brien-Fleming-like boundaries. Through its rigorous design and targeted approach, the LEVEL trial aims to establish whether ¹⁷⁷Lu-edotreotide can serve as a new standard-of-care treatment for patients with advanced lung and thymic NETs, potentially expanding therapeutic options in this challenging disease setting.

Source:bmccancer.biomedcentral.com/articles/10.1186/s12885-025-13941-3