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Treatment with 177Lu-edotreotide was linked to improvements in PFS and ORR across subgroups of patients with SSTR-positive GEP-NETs.
Treatment with 177Lu-edotreotide (ITM-11) was associated with improvements in progression-free survival (PFS) and overall response rate (ORR) compared with everolimus in patients with grade 1 or 2, somatostatin receptor (SSTR)–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to data from a subgroup analysis of the phase 3 COMPETE trial (NCT03049189) presented at the 2025 NANETS Annual Symposium.1,2
Among the subgroups analyzed, a statistically significant improvement in PFS was observed in patients treated in the second line of therapy (HR, 0.678; 95% CI, 0.47-0.98; P = .039). The median PFS in this subgroup was 23.9 months for 177Lu-edotreotide (n = 177) compared with 14.1 months for everolimus (n = 85). Numerical trends favoring the 177Lu-edotreotide arm without statistical significance were observed in other subgroups, including patients with grade 1 tumors (HR, 0.657; 95% CI, 0.42-1.04; P = .071), patients with grade 2 tumors (HR, 0.635; 95% CI, 0.37-1.10; P = .102), patients with gastroenteric NETs (GE-NETs; HR, 0.636; 95% CI, 0.38-1.08; P = .090), patients with pancreatic NETs (P-NETs; HR, 0.699; 95% CI, 0.45-1.09; P = .114), and patients treated in the first-line setting (HR, 0.598; 95% CI, 0.25-1.45; P = .249).
ORRs were also consistently higher with 177Lu-edotreotide across these 6 prespecified subgroups. In patients with grade 1 tumors, the ORR was 15.8% with 177Lu-edotreotide (n = 104) vs 3.3% with everolimus (P = .018), and in those with grade 2 tumors, the ORR was 28.3% vs 3.1% for 177Lu-edotreotide (n = 102) and everolimus (n = 37), respectively (P = .003). In patients with gastroenteric NETs, the ORR was 6.0% for 177Lu-edotreotide (n = 88) vs 5.0% for everolimus (n = 43; P = 1.00), and those with pancreatic NETs experienced an ORR of 33.3% with 177Lu-edotreotide (n = 119) vs 3.6% for everolimus (n = 59; P < .001). Patients treated in the first line achieved an ORR of 17.9% with 177Lu-edotreotide (n = 30) compared with 5.9% with everolimus (n = 17; P = .385), and those treated in the second line experienced ORRs of 22.5% and 3.8%, respectively (P < .001).
“The COMPETE trial is the first international phase 3 study that demonstrated radioligand therapy with DRUG improved median PFS significantly over [everolimus],” lead study author Jaume Capdevila, MD, PhD, a senior researcher in the Upper Gastrointestinal and Endocrine Tumor Group at Vall d'Hebron Institut d’Oncologia in Barcelona, Spain, said in a presentation of the data.
Prior data from the phase 3 study demonstrated that patients treated with 177Lu-edotreotide (n = 207) experienced a median PFS of 23.9 months (95% CI, 18.7-30.0) compared with 14.1 months (95% CI, 9.2-20.9) for those given everolimus (n = 102; HR, 0.67; 95% CI, 0.48-0.95; P = .022), meeting the study’s primary end point.3
Additionally, 177Lu-edotreotide generated a median overall survival (OS) of 63.4 months compared with 58.7 months for everolimus; although numerically higher, this difference did not reach statistical significance (HR, 0.78; 95% CI, 0.5-1.1; P = .206).
The prospective, controlled, open-label, multicenter trial enrolled patients at least 18 years of age with well-differentiated, non-functional GE-NETs or functional/non-functional P-NETs that were grade 1 or 2 with a Ki-67 status of no more than 20%. Patients needed to have unresectable or metastatic, progressive, SSTR-positive disease per imaging. Investigators enrolled patients who were treatment naive or those who experienced disease progression under prior therapy.
Patients we randomly assigned 2:1 to receive 177Lu-edotreotide at 7.5 ± 0.7 GBq once every 3 months for 4 cycles, or everolimus at 10 mg once per day. Key stratification factors included primary tumor origin and prior therapy.
Along with the primary end point of PFS, secondary end points included ORR, OS, disease control rate, duration of disease control, health-related quality of life, and safety/tolerability.
Patients in the 177Lu-edotreotide arm had a median age of 65.0 years (range, 22-86) compared with 61.0 years (range, 26-85) in the everolimus arm. The majority of patients were male (177Lu-edotreotide, 53.1%; everolimus, 56.9%), had grade 1 tumors (50.2%; 61.8%), had P-NETs (57.5%; 57.8%), and received 1 prior line of therapy (85.5%; 83.3%). Notably, among patients with P-NETs, 83.2% of patients in the 177Lu-edotreotide arm (n = 119) had non-functional P-NETs, and 16.8% had function P-NETs. In the everolimus arm (n = 59), 86.4% of patients with P-NETs had non-functional tumors, and 13.6% had functional tumors.
Among patients with grade 1 tumors, the median OS was not reached (NR) in both the 177Lu-edotreotide and everolimus arms (HR, 0.899; 95% CI, 0.52-1.35; P = .702), and in those with grade 2 tumors, the median OS was 56.7 months for 177Lu-edotreotide vs 41.4 months for everolimus (HR, 0.618; 95% CI, 0.36-1.07; P = .082).
For patients with GE-NETS, the median OS was 63.4 months with 177Lu-edotreotide compared with 58.7 months with everolimus (HR, 0.926; 95% CI, 0.51-1.67; P = .799), and in those with P-NETs, the median OS was 65.7 months vs 49.3 months, respectively (HR, 0.753; 95% CI, 0.46-1.24; P = .263).
Among patients treated in the first line, the median OS was 57.4 months for 177Lu-edotreotide vs NR for everolimus (HR, 5.128; 95% CI, 1.16-22.03; P = .016), and in the second line, the median OS was 63.4 months vs 43.4 months, respectively (HR, 0.618; 95% CI, 0.41-0.92; P = .018).
Disclosures: Capdevila reported receiving grant and/or research support from Advanced Accelerator Applications, AstraZeneca, Amgen, Bayer, Eisai, Gilead, ITM, Novartis, Pfizer, and Roche; serving as a member of a speaker bureau for Advanced Accelerator Applications, Advanz Pharma, Amgen, Bayer, Eisai, Esteve, Exelixis, Hutchmed, Ipsen, ITM, Lilly, Merck Serono, Novartis, Pfizer, Roche, and Sanofi; serving as an advisory board member for Amgen, Bayer, Eisai, Steve, Exelixis, Ipsen, ITM, Lilly, Novartis, and Roche; and serving in a leadership role and chair for the Spanish Task Force for Neuroendocrine and Endocrine Tumours Group.
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