Pivotal phase III COMPOSE trial will compare ¹⁷⁷Lu-edotreotide with best standard of care for well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumors.

Abstract

TPS514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which represent approximately 70% of NETs, frequently develop metastatic disease with limited treatment options. Current standard therapies for well-differentiated high grade 2 and grade 3 GEP-NETs include cytoreductive procedures, somatostatin analogues, molecular targeted therapies (everolimus or sunitinib), chemotherapy and peptide receptor radionuclide therapy (PRRT), with no specified sequence of use. PRRT may stabilize disease and induce objective tumor responses. This treatment uses radiolabeled somatostatin analogues to selectively target somatostatin receptor expressing (SSTR+) tumor cells. 177Lu-edotreotide is an innovative radiolabeled somatostatin analogue with a favorable safety profile and promising efficacy. Retrospective data in metastatic GEP-NETs treated with two or more 177Lu-edotreotide cycles demonstrated a progression free survival (PFS) of at least 30 months. The currently recruiting Phase III COMPETE trial compares the efficacy and safety of 177Lu-edotreotide, versus everolimus, in grade 1 and grade 2 GEP-NETs. Methods: COMPOSE (NCT04919226) is a prospective, randomized, controlled, open-label, multi-center Phase III study, in patients with well-differentiated high grade 2 and grade 3 (Ki-67 index 15−55%), SSTR+, GEP-NETs. This trial is to evaluate the efficacy, safety and patient-reported outcomes of first- or second-line treatment with 177Lu-edotreotide PRRT compared to best standard of care. It aims to randomize 202 patients 1:1 to a defined number of cycles of 177Lu-edotreotide or an active comparator (either chemotherapy [CAPTEM or FOLFOX] or everolimus, according to investigator´s choice). The primary endpoint is PFS, assessed every 12 weeks until disease progression (RECIST v1.1), or death, whichever occurs earlier. Secondary outcomes include overall survival, assessed up to 2 years after disease progression. Study recruitment for COMPOSE commenced in September 2021. It is expected that COMPOSE will inform optimal treatment options for patients with well-differentiated high grade 2 and grade 3 SSTR+ GEP-NETs, including for first-line therapy. Clinical trial information: NCT04919226.

Recurring Pancreatic Neuroendocrine Tumor: Timing and Pattern of Recurrence and Current Treatment

“…To date, randomized trials comparing head-to-head treatments for metastatic PanNET are lacking, yet trials are ongoing. 18,19 In our real-world study, recurrence of PanNET was managed with sequential use of different types of treatment in ∼60% of cases, and in one third of patients' systemic chemotherapy was used; it should be noted that, compared with patients with metastatic disease at diagnosis, recurring patients are usually diagnosed during radiologic surveillance and might present with lower volume of disease. Whether earlier intervention leads to better outcomes is unknown and side effects of therapy should always be weighed with biology of the disease when deciding on timing of treatment.…”

“…Like patients with initial metastatic disease, these patients should be approached by considering the PanNET proliferative activity, tumor bulk, and the presence of hormonal syndrome. To date, randomized trials comparing head-to-head treatments for metastatic PanNET are lacking, yet trials are ongoing 18,19 . In our real-world study, recurrence of PanNET was managed with sequential use of different types of treatment in ∼60% of cases, and in one third of patients’ systemic chemotherapy was used; it should be noted that, compared with patients with metastatic disease at diagnosis, recurring patients are usually diagnosed during radiologic surveillance and might present with lower volume of disease.…”

Sequencing of Therapies in Progressive Neuroendocrine Tumors

“…7,10 The ongoing COMPETE trial is currently looking at this very question in GEPNETs, with one group being randomized to 177 Lu-edotreotide PRRT and the other to everolimus. 16 For patients with pancreatic NETs, there are more choices available, which include PRRT, sunitinib, everolimus, and capecitabine/temozolomide, which may help explain why over three quarters of patients initially received TT/CT instead of PRRT in this study. Greater uncertainty remains in patients with higher-grade tumors, who did not appear to derive as much benefit from PRRT.…”

“…That question may be answered by the COMPOSE trial, comparing 177 Lu-edotreotide PRRT to best standard of care (including all TT and CT) in aggressive grade 2 and grade 3 GEP-NETs. 16 Another relevant trial just opening is Alliance for Clinical Trials in Oncology A022001 (ComPareNET; NCT05247905), which will randomize patients with progressive, advanced, well-differentiated grade 1-3 pancreatic NETs to PRRT ( 177 Lu-DOTATATE x 4 cycles) or 12 cycles of capecitabine/temozolomide.…”