Experimental therapy outperforms approved treatment in PNET trial
177Lu-edotreotide shows longer progression-free survival vs. everolimus
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The experimental therapy 177Lu-edotreotide outperformed the approved treatment everolimus in prolonging progression-free survival in people with pancreatic neuroendocrine tumors (PNETs), according to a new analysis of a Phase 3 clinical trial.
ITM Isotope Technologies Munich SE, the company developing 177Lu-edotreotide, shared the findings at the 23rd Annual Meeting of the European Neuroendocrine Tumor Society (ENETS), held earlier this week in Krakow, Poland.
“These additional results from our Phase 3 COMPETE trial provide important insights into treatment options for patients with pancreatic NETs, and further enhance the robust clinical data of 177Lu-edotreotide,” said Celine Wilke, MD, chief medical officer of ITM, in a company press release.
Phase 3 trial compares experimental therapy with everolimus
The Phase 3 COMPETE trial (NCT03049189) enrolled more than 300 people with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) — hormone-producing tumors that can develop in the pancreas or digestive tract. To be eligible, patients had to have Grade 1 or Grade 2 tumors, meaning the cancer cells grow slowly or moderately quickly, and their tumors had to express a protein called somatostatin receptor (SSTR). 177Lu-edotreotide, also known as ITM-11, is designed to deliver a radioactive molecule directly to cancer cells that express this receptor.
Participants in COMPETE were randomly assigned to receive 177Lu-edotreotide or everolimus, an approved targeted therapy sold as Afinitor, among others. The study’s main goal was to determine whether 177Lu-edotreotide could improve progression-free survival (PFS), the length of time patients live without their cancer worsening.
ITM previously announced that the trial met its primary endpoint, with a clinically and statistically significant improvement in progression-free survival. Median PFS was nearly two years with 177Lu-edotreotide, compared with 14.1 months with everolimus. The proportion of patients whose tumors shrank after treatment was also higher with 177Lu-edotreotide than with everolimus (21.9% vs 4.2%).
In a prespecified subgroup analysis, researchers looked specifically at outcomes among participants with pancreatic tumors, who made up just over half of all patients in the trial.
Analysis focuses on patients with pancreatic tumors
Of 178 patients with PNETs, 150 (84.3%) had nonfunctional tumors, meaning they did not produce hormones that cause symptoms. The remaining 28 (15.7%) had functional tumors, which release excess hormones and may lead to symptoms such as hypoglycemia, diarrhea, or peptic ulcers.
Among these patients, median progression-free survival was longer with 177Lu-edotreotide than with everolimus (24.5 vs. 14.7 months). The overall response rate, meaning the proportion of patients whose tumors shrank after treatment, was also higher with 177Lu-edotreotide (33.3% vs. 3.6%). Specifically, the response rate with ¹⁷⁷Lu-edotreotide was at least 30% in patients with nonfunctional tumors, regardless of whether it was used as an earlier or later treatment.
Median overall survival was numerically higher with 177Lu-edotreotide than everolimus (65.7 vs. 49.3 months), although these data continue to evolve because some patients remain alive.
Safety data showed that serious adverse events were reported less frequently in patients receiving 177Lu-edotreotide than in those receiving everolimus (29.1% vs. 43.1%). Patients receiving 177Lu-edotreotide also had slightly lower rates of treatment-related side effects, according to investigators (83.8% vs. 96.6%).
“Given that the data on peptide receptor radionuclide therapy in pancreatic NETs has been limited to date, we are encouraged by the activity of 177Lu-edotreotide observed in this prespecified exploratory subgroup of patients with Grade 1 or 2 pancreatic NETs, who represented approximately 58% of trial participants,” said Thomas Walter, MD, PhD, professor of gastroenterology at Hospices Civil of Lyon in France.
