[177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study.

• DOI: 10.1200/jco.2024.42.3_suppl.lba588
• Publication Date: 2024-01-22T21:12:58Z
• Authors: Simron Singh; Daniel M. Halperin; Sten Myrehaug; Ken Herrmann; Marianne Pavel; Pamela L. Kunz; Beth Chasen; Jaume Capdevila; Salvatore Tafuto; Do-Youn Oh; Changhoon Yoo; Stephen Falk; Thorvardur Ragnar...; Ilya Folitar; Yufen Zhang; Paola Santoro; Paola Aimone; Wouter W. de Herder; Diego Ferone
• Keywords: Clinical endpoint; Radionuclide therapy; Progression-free survival

LBA588 Background: Currently, there is no universally accepted first line (1L) therapy for higher grade, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and an unmet medical need remains in these patients (pts). Radioligand (RLT) innovative cancer treatment that crosses the traditional domains of systemic, radiation or surgical therapies. The Phase 3 NETTER-2 study (NCT03972488) evaluated [ 177 Lu]Lu-DOTA-TATE (hereafter Lu-DOTATATE) as 1L pts with Grade (G) 2 G3 advanced GEP-NETs. This trial to assess RLT any solid tumor. Methods: Eligible were newly diagnosed somatostatin receptor-positive high G2 (Ki-67 ≥10% ≤55%) GEP-NETs within last 6 months prior enrollment. Pts randomized (2:1) receive 4 cycles Lu-DOTATATE (4 × 7.4 GBq) plus 30 mg octreotide long-acting release (LAR) at 8-weekly intervals during then every weeks ( arm), 60 LAR (control stratified by grade (G2 vs G3) tumor origin (pancreas other). primary endpoint was progression-free survival (PFS), centrally assessed using RECIST 1.1. Objective response rate (ORR), a key secondary endpoint, tested hierarchically after PFS. Results: Overall, 226 (n = 151) control 75) arms. Most originated pancreas (54.4%) small intestine (29.2%); reported 35.0% pts. Median cumulative dose 29.2 GBq, 87.8% receiving all doses. PFS (95% confidence interval [CI]) significantly prolonged ~14.3 from 8.5 (7.7, 13.8) arm 22.8 (19.4, not estimable) arm; hazard ratio 0.276 CI: 0.182, 0.418; p < 0.0001). ORR (43.0%) (9.3%); odds 7.81 3.32, 18.4; results consistent across pre-specified demographic prognostic subgroups. Among adverse events special interest RLT, G3/4 leukopenia, anemia thrombocytopenia occurred ≤3 each arm. One case myelodysplastic syndrome arm). Conclusion: demonstrated clinically meaningful ORR, compared high-dose LAR, Safety established profile Lu-DOTATATE. demonstrate efficacy malignancy will change clinical practice. Further investigations therapeutic option other settings warranted. Clinical information: NCT03972488 .