Background
Phase 3, open-label, superiority trial (49 centers, 14 countries) of peptide receptor radionuclide therapy with [177Lu]Lu-edotreotide (ITM-11) versus everolimus in grade 1–2, inoperable/progressive, somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NET). 309 patients randomized 2:1.
Results
Interventions and follow up: Arm A: [177Lu]Lu-edotreotide (PRRT) IV (n=207).
Arm B: Everolimus 10 mg PO once daily (n=102).
Primary endpoint: Progression-free survival (PFS).
mFollow up: NR.
Results: PFS: 23.9 vs 14.1 mo; HR 0.67 (95% CI 0.48–0.95).
OS: NR (immature).
ORR: NR in primary report.
Arm B: Everolimus 10 mg PO once daily (n=102).
Primary endpoint: Progression-free survival (PFS).
mFollow up: NR.
Results: PFS: 23.9 vs 14.1 mo; HR 0.67 (95% CI 0.48–0.95).
OS: NR (immature).
ORR: NR in primary report.
Adverse events
Any TEAE: 82.5% (177Lu-edotreotide) vs 97.0% (everolimus).
Grade ≥3 breakdown: NR in primary report; overall treatment burden lower with PRRT.
Grade ≥3 breakdown: NR in primary report; overall treatment burden lower with PRRT.
Conclusions
First-line/progressive PRRT with [177Lu]Lu-edotreotide significantly prolonged PFS versus everolimus in SSTR-positive grade 1–2 GEP-NET, with a lower overall adverse-event burden, supporting radioligand therapy over everolimus in this setting.
Key Limitations
Open-label design; PFS primary with immature OS; everolimus (rather than a somatostatin analogue or alternative PRRT) as the sole comparator; a biologically heterogeneous GI-plus-pancreatic NET population; sequencing relative to other approved agents not addressed.
Clinical Context
Complements NETTER-1 and NETTER-2 ([177Lu]Lu-DOTATATE) in establishing PRRT as a core NET therapy, and provides randomized evidence favoring radioligand therapy over everolimus in SSTR-positive GEP-NET. [177Lu]Lu-edotreotide (ITM-11) is not yet FDA-approved.
References