Scholarlink

Background <p>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.</p> Methods <p>The LEVEL trial is a randomized, open-label, phase III international trial of <sup>177</sup>Lu-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.</p> <p>Eligible patients are randomly assigned 3:2 to 6 cycles of <sup>177</sup>Lu-edotreotide (total administered activity 7.5 ± 0.7&#xa0;GBq / cycle) or to oral everolimus 10&#xa0;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&#xa0;weeks until PD. Blood samples are analyzed at baseline, at 1<sup>st</sup> tumor assessment, and at PD for pharmacodynamic endpoints. Archival tumor tissue samples will be analyzed for ancillary studies.</p> <p>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).</p> <p>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.</p> Discussion <p>The LEVEL trial will investigate if <sup>177</sup>Lu-edotreotide has the potential to be incorporated as a standard treatment option for patients with NETs from the lung and Thymus.</p> Trial Registration <p>EU CT: 2022–502154-13–00 / <a href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</a>: NCT05918302 (June 23<sup>rd</sup>, 2023).</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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)

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月4日

查看全文
  • Jaume Capdevila,
  • Virginia Pubul,
  • Urbano Anido,
  • Thomas Walter,
  • Javier Molina-Cerrillo,
  • Teresa Alonso-Gordoa,
  • Rocio Garcia-Carbonero,
  • Maria San-Roman-Gil,
  • Belen Llana,
  • Paula Jimenez-Fonseca,
  • Marta Benavent Viñuales,
  • Catherine Ansquer,
  • Eric Baudin,
  • Come Lepage,
  • Maribel del Olmo-García,
  • José Carlos Ruffinelli,
  • Amandine Beron,
  • Magalie Haissaguerre,
  • Emmanuel Deshayes,
  • David Taïeb,
  • Sergio Baldari,
  • Maddalena Sansovini,
  • Sara Cingarlini,
  • Angelina Filice,
  • Francesco Panzuto,
  • Rosa Álvarez-Álvarez,
  • Laurence Lousberg,
  • Frank Aboubakar Nana,
  • Jorge Hernando,
  • Alejando García-Álvarez,
  • Amparo García-Burillo,
  • Guillermo Villacampa,
  • Timon Vandamme,
  • Nicola Fazio,
  • Alice Durand

摘要

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).