BACKGROUND Peptide receptor radionuclide and targeted therapy are both approved treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs), but clinical evidence for preferred sequencing is scarce. The COMPETE trial evaluated the efficacy and harms of peptide receptor radionuclide therapy (177LuLu-edotreotide) versus targeted molecular therapy (everolimus) in patients with advanced, progressive, somatostatin receptor-positive GEP NETs. METHODS This phase 3, open-label, superiority trial included patients aged 18 years or older with treatment-naive or previously treated unresectable or metastatic (or both) grade 1-2 GEP NETs. Patients were enrolled from 49 specialist neuroendocrine tumour treatment centres across 14 countries in Africa, Europe, North America, and Oceania and randomised (2:1) to intravenous 177LuLu-edotreotide (7·5 ± 0·7 GBq every 3 months, maximum four cycles) or oral everolimus (10 mg/day) for up to 30 months. Random assignment was via a central, web-based randomisation system (block size of 6) and stratified by primary tumour origin and previous therapy. The primary endpoint was progression-free survival, assessed via blinded independent central review in all randomly assigned patients at 30 months. Harms were assessed in all enrolled patients who received at least one dose of a study drug. This study was registered with ClinicalTrials.gov (NCT03049189) and is no longer recruiting. FINDINGS Between April 13, 2017, and June 20, 2022, 324 patients were enrolled and 309 patients (including 168 54% male patients and 141 46% female patients) were randomly assigned to treatment: 207 to the 177LuLu-edotreotide group and 102 to the everolimus group. The median follow-up for progression-free survival was 27·5 months (IQR 19·6-30·4) for the 177LuLu-edotreotide group and 21·2 months (8·9-29·4) for the everolimus group. Median progression-free survival was significantly longer with 177LuLu-edotreotide versus everolimus (23·9 months 95% CI 18·7-30·0 vs 14·1 months 9·2-20·9; stratified hazard ratio 0·67 95% CI 0·48-0·95; p=0·022). Treatment-related adverse events occurred in 178 (82%) of 217 patients in the 177LuLu-edotreotide group and 96 (97%) of 99 patients in the everolimus group. 40 (18%) patients in the 177LuLu-edotreotide group and 40 (40%) in the everolimus group had at least one treatment-related grade 3-4 adverse event. The most common treatment-related adverse events in the 177LuLu-edotreotide group were diarrhoea and nausea (both 79 36% patients) and asthenia (66 33% patients), whereas those in the everolimus group were diarrhoea (45 45% patients), asthenia (36 36% patients), and anaemia (27 27% patients). No treatment-related deaths occurred in either study group. INTERPRETATION 177LuLu-edotreotide led to statistically significant and clinically meaningful improvements in progression-free survival. Efficacy and harms results support the use of 177LuLu-edotreotide in early lines of therapy in patients with advanced, progressive GEP NETs. FUNDING ITM Solucin.
Walter et al. (Wed,) studied this question.