Dr Capdevila on "Practice-Changing" COMPETE Trial in GEP-NETs

Jaume Capdevila, MD, Vall d'Hebron Hospital, discusses the final analysis of the phase 3 COMPETE trial (NCT03049189). Data from the trial, presented at both the 2025 ESMO Congress and NANETS Symposium, demonstrated that the radiopharmaceutical ITM-11 (¹⁷⁷Lu-edotretide) significantly outperformed everolimus across multiple efficacy end points for patients with well-differentiated, unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

The trial successfully met its primary end point, showing a clinically and statistically significant improvement in progression-free survival (PFS). The median PFS for patients treated with ITM-11 was 23.9 months, substantially longer than the 14.1 months recorded for the everolimus group (HR, 0.67; P =.022). Furthermore, the secondary end point of overall survival (OS) was also identified as being higher in the ITM-11 arm. The superior efficacy was underscored by a dramatically higher overall response rate (ORR), which was 21.9% for ITM-11 compared with just 4.2% for everolimus (P <.0001).

Subgroup analyses provided further support, with ITM-11 showing a pronounced benefit in patients withgGrade 2 tumors, where the median PFS reached 21.7 months vs 9.2 months with everolimus (P =.0003).

In terms of safety, ITM-11 proved to be more tolerable. While drug-related adverse events (AEs) were reported in 82% of the ITM-11 group, this was less than the 97% in the everolimus group. Crucially, AEs leading to premature study discontinuation were substantially lower for ITM-11 (1.8% vs. 15.2% for everolimus). The trial’s dosimetry data also validated the treatment's targeted mechanism, showing high tumor uptake with minimal exposure to healthy organs, which may allow for improved individualized patient management. The positive results from COMPETE have influenced the design of subsequent radiopharmaceutical trials, including the phase 3 COMPOSE study for more aggressive GEP-NETs.