COMPETE trial: Peptide receptor radionuclide therapy (PRRT) with 177Lu-edotreotide vs. everolimus in progressive GEP-NET

Background: There are only limited treatment options for metastasized gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Current standard therapies include somatostatin analogs and targeted drugs such as everolimus and sunitinib. While these treatments rarely induce objective tumor remission, disease stabilization may be achieved for limited periods of time. Median PFS with everolimus in prospective phase III trials is 11 months. A subset of patients may have a benefit of systemic chemotherapy. PRRT has recently emerged as a promising option providing more durable response and potentially higher objective response rates. This therapy uses IV-infused radiolabeled somatostatin analogues to deliver radioactivity directly to metastases, destroying tumor cells but sparing most of the surrounding tissue. A first retrospective study on 177LuEdotreotide PRRT in metastasized GEP-NET reported a median PFS of 34.5 months in patients who received ≥ 2 treatment cycles. Trial design: COMPETE is a prospective, randomised, controlled, open-label, multicentre phase III study to evaluate the efficacy and safety of 177Lu-Edotreotide PRRT in comparison with everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+) GEP-NET. The study is ongoing in 11 countries & 40 centres worldwide, and currently recruiting patients. 300 patients will be randomized with progressive GEP-NET: 200 will receive max. 4 cycles of 177Lu-Edotreotide PRRT (7.5 GBq/ cycle) every 3 months or until diagnosis of progression; 100 will receive 10 mg everolimus daily for 24 months, or until diagnosis of progression. Study duration per patient will be 24 months. The primary endpoint is PFS. Diagnosis of progression and hepatic tumor burden will be established based on radiological information from morphological imaging (MRI and/or CT) according to RECIST 1.1. Key secondary endpoints are objective response rate (ORR), defined as%of patients achieving partial or complete response (PR/CR) as best outcome, and median duration of disease control (mDDC). Other secondary variables include safety and tolerability, dosimetry measures, overall survival, and quality of life.