At the NANETs 2025 Multidisciplinary NET Medical Symposium, investigators presented new efficacy findings from the COMPETE phase 3 trial comparing ¹⁷⁷Lu-edotreotide, a radiolabeled somatostatin analog, against everolimus, a targeted mTOR inhibitor, in patients with progressive, somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The results reinforce the growing role of peptide receptor radionuclide therapy (PRRT) in the management of well-differentiated NETs.

The trial enrolled 309 patients across multiple international centers and randomized them 2:1 to receive ¹⁷⁷Lu-edotreotide (7.5 GBq every 12 weeks for up to 4 cycles) or everolimus (10 mg daily) until disease progression or unacceptable toxicity. Eligible participants had inoperable, grade 1 or 2 GEP-NETs (Ki-67 ≤20%) and documented radiologic progression.

By blinded independent central review, median PFS was 23.9 months with ¹⁷⁷Lu-edotreotide compared to 14.1 months with everolimus (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.48 to 0.95; P = .0223). The objective response rate was also significantly higher at 21.9% vs 4.2% (P <.0001), reflecting greater tumor shrinkage and disease control with radioligand therapy. 

Preliminary overall survival (OS) data showed a numerical improvement with ¹⁷⁷Lu-edotreotide (63.4 months) vs everolimus (58.7 months) though survival outcomes remain immature (HR, 0.83; 95% CI 0.57 to 1.21; P = .3230).

Post hoc subgroup analyses demonstrated consistent benefits across clinically relevant subpopulations. Among grade 1 tumors, median PFS was 24.5 months vs 17.4 months with everolimus, while grade 2 tumors achieved 21.6 months vs 10.6 months, respectively. Patients with pancreatic NETs experienced particularly strong responses (median PFS, 24.5 months; ORR, 33.3%), while those with gastroenteric NETs achieved median PFS of 23.9 months and ORR of 6%. Outcomes were also favorable for both treatment-naïve and previously treated patients, highlighting ¹⁷⁷Lu-edotreotide’s broad applicability.

Investigators emphasized that ¹⁷⁷Lu-edotreotide offers a statistically and clinically meaningful improvement in disease control compared with everolimus, maintaining a consistent benefit across tumor subgroups and treatment histories. Despite ongoing follow-up for OS, the findings position ¹⁷⁷Lu-edotreotide as a potential first-line radiopharmaceutical option for patients with advanced, somatostatin receptor–positive GEP-NETs and high unmet therapeutic needs.

Source:

Capdevila J, Jann H, Ansquer C, et al. Efficacy of 177Lu-edotreotide vs everolimus in patients with grade 1 or grade 2 GEP-NETs: Phase 3 COMPETE trial (post hoc subgroup analyses). Presented at the NANETs 2025 Multidisciplinary NET Medical Symposium; October 23-25, 2025. Austin, Texas. Abstract ID 33388