The COMPETE trial

In this video, Prof Dr Ivan Borbath, digestive oncologist at the Cliniques Universitaires Saint-Luc in Brussels discusses the absolute highlight from ENETS 2025: the COMPETE trial. In fact, this presentation marks the first primary read out of a large, international, randomized, phase 3 trial ever to be presented at an ENETS conference.

COMPETE is the first phase 3 trial to directly compare peptide receptor radionuclide therapy (PRRT) as monotherapy to an approved targeted therapy in the 1^st or 2^nd line treatment of patients with a grade 1 or 2 neuroendocrine tumors of gastroenteric or pancreatic origin (GEP-NET). To this end, the study randomly assigned (2:1) 309 patients with an inoperable, progressive, grade 1 or 2 (Ki-67 ≤20%) somatostatin receptor (SSTR)-positive GEP-NET to receive ¹⁷⁷Lu-edotreotide every three months for up to four cycles, or everolimus 10 mg daily for up to 30 months, or until disease progression. Patients were stratified according to the primary tumour origin and the prior use of a somatostatin analogue (SSA) (1^st vs. 2^nd line). The two arms in the study were well balanced with approximately 85% of patients being previously treated with a SSA.

The study convincingly met its primary endpoint by showing a significantly longer median progression-free survival (PFS) for ¹⁷⁷Lu-edotreotide compared to everolimus at 23.9 and 14.1 months, respectively. This corresponds to a 33% lower risk of disease progression or death for patients treated with ¹⁷⁷Lu-edotreotide (HR[95%CI]: 0.67[0.48-0.95]; p= 0.022). Data for overall survival (OS) were immature, but indicate a numerical benefit for ¹⁷⁷Lu-edotreotide, with a median OS of 63.4 months as compared to 58.7 months for everolimus (HR[95%CI]: 0.78[0.53-1.15]; p= 0.206).

Safety was in line with what could be expected, with the ¹⁷⁷Lu-edotreotide treatment being associated with a treatment-emergent adverse event rate of 82.5% as compared to 97.0% in the everolimus arm. Corresponding rates if treatment-emergent adverse events of grade ≥3 were reported at 48% and 63.7%, respectively. Of note, one case of (grade 2) treatment-emergent MDS was reported in the ¹⁷⁷Lu-edotreotide arm.

In conclusion, the COMPETE trial shows that ¹⁷⁷Lu-edotreotide significantly delays disease progression compared to everolimus in patients with grade 1/2 GEP-NETs. Moreover, this clinical benefit was accompanied by a more favorable safety profile, marking PRRT as a potential new standard of care in this setting.