177Lu-edotreotide Improves PFS, OS Over Everolimus for SSTR-Positive GEP-NETs

New data from the phase 3 COMPETE trial point to the efficacy of the radiotherapy agent ¹⁷⁷Lu-edotreotide for the treatment of patients with grade 1 or 2 somatostatin receptor (SSTR)–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). ¹⁷⁷Lu-edotreotide is an IV therapy composed of non-carrier–added lutetium-177,  a therapeutic β-emitting radioisotope, and edotreotide, a synthetic SSTR agonist.

The COMPETE trial consisted of 309 patients with inoperable, progressive grade 1 or 2 SSTR-positive GEP-NETs. The primary objectives were efficacy and safety of ¹⁷⁷Lu-edotreotide compared with everolimus. ¹⁷⁷Lu-edotreotide is the first radiopharmaceutical that contains non-carrier-added lutetium, which has greater isotopic purity than carrier-added lutetium, to be evaluated as treatment for patients with GEP-NETs .

A total of 207 patients received 7.5 GBq of ¹⁷⁷Lu-edotreotide with a nephroprotective amino acid solution every 3 months for up 4 cycles, and 102 patients received everolimus 10 mg daily for up to 30 months or until disease progression occurred. To enhance safety and efficacy monitoring, dosimetry was used to determine the absorbed treatment dose in tumors compared with healthy tissue.

The primary objective of median progression-free survival (PFS) was significantly longer for patients treated with ¹⁷⁷Lu-edotreotide than for those treated with everolimus (23.9 vs 14.1 months; P=0.022; hazard ratio [HR], 0.67; 95% CI, 0.48-0.95). The secondary end point of interim median overall survival (OS) was also longer, but not conclusive, for patients treated with ¹⁷⁷Lu-edotreotide than for those treated with everolimus (63.4 vs 58.7 months; P=0.206; HR, 0.78; 95% CI, 0.5-1.1).

A lower number of patients experienced treatment-emergent adverse events (TEAEs) related to study medication with ¹⁷⁷Lu-edotreotide versus everolimus (82.5% vs 97.0%). One grade 2 serious TEAE, myelodysplastic syndrome, related to ¹⁷⁷Lu-edotreotide was reported, and there were no unforeseen TEAEs.

Additional data from COMPETE, including objective response rate, subgroup analyses, quality-of-life assessments, and dosimetry, are currently being evaluated. ¹⁷⁷Lu-edotreotide is also currently being studied for the treatment of well-differentiated, aggressive grade 2 or 3, SSTR-positive GEP-NETs.