[177Lu]Lu-DOTA-TATE plus long-acting octreotide in patients with newly diagnosed, advanced, grade 2–3, gastroenteropancreatic neuroendocrine tumours: preplanned and post-hoc efficacy analyses from the randomised, phase 3 NETTER-2 trial

作者：Diego Ferone, Marianne Pavel, Ken Herrmann, Pamela L. Kunz, Sten Myrehaug, Daniel M. Halperin, Beth Chasen, Jaume Capdevila, Amparo García-Burillo, Salvatore Tafuto, Secondo Lastoria, Do‐Youn Oh, Changhoon Yoo, S. Falk, Thorvardur R. Halfdanarson, Maddalena Sansovini, Laura Gérard, Emmanuel Deshayes, Angelina Filice, Ilya Folitar, Yufen Zhang, Wouter W. de Herder, Simron Singh · 发表于：EClinicalMedicine · 年份：2026 · DOI：10.1016/j.eclinm.2026.104109 · 研究领域：Neuroendocrine Tumor Research Advances、Lung Cancer Research Studies、Thyroid Cancer Diagnosis and Treatment

Background In the phase 3 NETTER-2 study, first-line [ 177 Lu]Lu-DOTA-TATE (hereafter 177 Lu-DOTATATE) significantly improved progression-free survival in patients with advanced, well-differentiated, higher grade 2–3 (Ki67 ≥10% and ≤55%), somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Median progression-free survival was 22·8 months (95% CI 19·4–not estimable [NE]) with 177 Lu-DOTATATE vs 8·5 months (7·7–13·8) in the control arm. Here, we report subgroup analyses, including preplanned assessments of efficacy by NET grade (G) and site of origin; further post-hoc analyses are reported in the main text. Methods In this open-label, parallel-group study, patients from nine countries were randomised 2:1 to receive four cycles of 177 Lu-DOTATATE plus octreotide long-acting repeatable (LAR) 30 mg every 8 weeks then octreotide LAR 30 mg every 4 weeks, or high-dose octreotide LAR 60 mg every 4 weeks. The primary endpoint (progression-free survival) was previously reported. Tumours were assessed at baseline, week 16, week 24, then every 12 weeks until disease progression or death. Preplanned subgroup analyses used blinded independent centrally reviewed data. The study is registered with ClinicalTrials.gov, NCT03972488, and is completed. Findings Between Jan 22, 2020, and Oct 13, 2022, 261 patients were screened; 35 were excluded due to screen failure, and 226 were randomised. 177 Lu-DOTATATE (n = 151) reduced risk of disease progression/death vs...