Breakthrough Clinical Results
ITM Isotope Technologies Munich SE announced that it will present further analysis from its completed Phase 3 COMPETE trial at the SNMMI 2025 annual meeting. The trial evaluated 177Lu-edotreotide (ITM-11) in patients with grade 1 or grade 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The presentation will cover 177Lu-edotreotide tumor uptake predictability using pre-therapeutic imaging. A satellite symposium will also discuss the GEP-NET treatment landscape, COMPETE trial results, and dosimetry standardization. The COMPETE trial met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) for 177Lu-edotreotide compared to everolimus.
Key Highlights
- Presentation of COMPETE trial data at SNMMI 2025.
- Analysis of 177Lu-edotreotide tumor uptake predictability.
- Satellite symposium on GEP-NET treatment, COMPETE results, and dosimetry.
- COMPETE trial met its primary endpoint, showing improved PFS for 177Lu-edotreotide.
Study Design Parameters
Several clinical trials have investigated various aspects of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs), exploring diagnostic tools, treatment efficacy, and prognostic factors. Here's a summary of study design parameters and endpoints from key trials:
1. CLARINET Study: * Design: Randomized, double-blind, placebo-controlled * Intervention: Lanreotide Autogel * Primary Endpoint: Progression-free survival (PFS) * Secondary Endpoints: Overall survival (OS), symptom control, hormone levels * Key Findings: Lanreotide significantly prolonged PFS in patients with metastatic GEP-NETs.
2. NETTER-1 Trial: * Design: Randomized, international, phase III * Intervention: 177Lu-DOTATATE vs. high-dose octreotide LAR * Primary Endpoint: PFS * Secondary Endpoints: OS, tumor response, safety * Key Findings: 177Lu-DOTATATE demonstrated superior PFS and a higher response rate compared to high-dose octreotide in patients with progressive, metastatic midgut NETs.
3. PROMID Study: * Design: Randomized, controlled * Intervention: Octreotide LAR vs. placebo * Primary Endpoint: Time to tumor progression * Secondary Endpoints: Symptom control, hormone levels * Key Findings: Octreotide LAR significantly prolonged time to tumor progression in patients with metastatic midgut NETs.
4. RADIANT-4 Trial: * Design: Randomized, double-blind, placebo-controlled, phase III * Intervention: Everolimus vs. placebo * Primary Endpoint: PFS * Secondary Endpoints: OS, tumor response, safety * Key Findings: Everolimus significantly prolonged PFS in patients with advanced, progressive pancreatic NETs.
5. Phase III Trial in Japan (jRCT1031200023): * Design: Randomized, phase III * Intervention: Everolimus plus lanreotide vs. everolimus monotherapy * Primary Endpoint: PFS * Secondary Endpoints: OS, response rate, disease control rate, adverse events * Key Findings: This trial is ongoing and aims to confirm the superiority of combined everolimus and lanreotide therapy over everolimus monotherapy in patients with unresectable or recurrent gastroenteropancreatic NETs with poor prognostic factors.
Other Notable Studies: * Several retrospective cohort studies have investigated the prognostic value of hematologic markers, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), in GEP-NETs. These studies have generally found that elevated NLR and PLR are associated with poorer prognosis. * A cross-sectional case-control study examined the nutritional status and adherence to the Mediterranean Diet in GEP-NET patients, finding that patients with more aggressive disease had lower adherence to the diet and poorer nutritional status. * Studies have also explored the use of various imaging modalities, such as somatostatin receptor scintigraphy (SRS), somatostatin receptor PET (SSTR PET/CT), 18F-DOPA PET/CT, and 18F-FDG PET/CT, in the diagnosis and staging of GEP-NETs.
Overall, the choice of study design and endpoints in GEP-NET trials depends on the specific research question being addressed. Randomized controlled trials are considered the gold standard for evaluating treatment efficacy, while observational studies can provide valuable information on prognosis and the impact of various factors on patient outcomes.
Incidence and Prevalence
The incidence and prevalence of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) are increasing globally, although variations in reporting and classification make precise comparisons challenging. Several studies highlight this trend:
- A study using the SEER database found a 6.4-fold increase in the age-adjusted incidence rate of GEP-NETs from 1975 to 2015, with an annual percentage change (APC) of 4.98%. Rectal GEP-NETs showed the most significant increase (APC 6.43%). Localized GEP-NETs and G1 GEP-NETs also had the highest increase in incidence.
- Another study analyzing SEER data from 1975-2012 found a continuous increase in incidence, particularly in adults aged 40-69 (APC 4-6% per year). The highest overall incidence rates were in adults aged 70-84.
- A systematic review of population-based studies confirmed the increasing global incidence of GEP-NENs over recent decades, with data from various regions supporting this pattern. However, variations in classification, grading, and reporting make direct comparisons difficult.
- A study from two Swiss regions (1976-2016) showed an annual increase in GEP-NET incidence of 1.7% in men and 1.3% in women.
- A review of global trends found steadily rising incidence rates in North America, Asia, and Europe, with the increase most pronounced in North America. Regional variations in primary tumor site distribution were also observed.
- An earlier study (1973-2007) reported a 3.65-fold increase in GEP-NET incidence in the USA and a 3.8- to 4.8-fold increase in the UK. Gastric and rectal NETs showed the greatest increase, while small intestine NETs had the smallest.
While increased healthcare utilization contributes to the rising incidence, it doesn't fully explain the trend. Further research with standardized data collection and pathology grading is needed to identify other contributing factors.
While the provided text extensively discusses the use of 177Lu-DOTATATE (also referred to as 177Lu-octreotate or 177Lu-edotreotide/ ITM-11) in GEP-NETs, it does not mention any other indications for which this specific radioligand therapy is being trialled.
However, the text does mention combining 177Lu-octreotate with other therapies to improve treatment outcomes specifically for GEP-NETs. One study investigated the combination of 177Lu-octreotate with Hsp90 inhibitors like ganetespib, demonstrating synergistic anti-tumor effects in small intestinal neuroendocrine tumor (SINET) models. Another study explored the combination of 177Lu-DOTATATE with low-dose capecitabine in advanced grade 1/2 GEP-NETs, but found no significant improvement in radiographic responses compared to 177Lu-DOTATATE alone. Further studies are suggested to evaluate the potential role of this combination in high-grade NETs.
It's important to note that while 177Lu-DOTATATE itself isn't mentioned in trials for other indications in these texts, the concept of peptide receptor radionuclide therapy (PRRT) using other radioligands is a broader field. The principle of targeting somatostatin receptors with a radioactive payload could potentially be applied to other tumor types expressing these receptors, but this information is not present in the provided abstracts.