A recent study found that a combination of the mTOR inhibitor everolimus and the hormone-blocking drug lanreotide extended progression-free survival compared with everolimus alone for people with some types of neuroendocrine tumors in the pancreas or gastrointestinal tract. The research will be presented by Hijioka et al at the 2025 ASCO Gastrointestinal Cancers Symposium (Abstract 625).
Study Details
“The current standard of care for these patients, everolimus monotherapy, provides a limited progression-free survival of approximately 11 months, leaving significant room for improvement. Effective treatments for patients with a poor prognosis, such as those with high Ki67 levels or diffuse liver metastases, are lacking. Although combination therapies have shown promise in other cancer types, their potential in neuroendocrine tumors had not been fully explored. This study aimed to fill these gaps, improve prognosis for high-risk groups, and develop treatments that balance efficacy with safety and tolerability, ultimately advancing the standard of care for [neuroendocrine tumors] globally,” said lead study author Susumu Hijioka, MD, PhD, of the Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo.
Although rare, gastroenteropancreatic neuroendocrine tumors are the most common type of neuroendocrine tumor, with between 55% and 70% of all neuroendocrine tumors beginning in the pancreas or gastrointestinal tract.
This phase III study included patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors that could not be treated with surgery or that had recurred. The patients also had other risk factors suggesting a poor prognosis, including Ki67 levels between 5% and 20%.
There were 178 patients enrolled in the study; of these patients, 145 were randomly assigned to receive either everolimus alone (n = 72) or the combination treatment with everolimus and lanreotide (n = 73). Although all patients in this study were from Japan, the biological characteristics of neuroendocrine tumors—such as somatostatin receptor expression and Ki67 levels—are considered consistent across different populations worldwide.
Key Findings
The median progression-free survival was 11.5 months in the everolimus arm. In comparison, the combination regimen extended the median progression-free survival to 29.7 months (hazard ratio = 0.38, 99.91% confidence interval = 0.15–0.96, P = .00017). In the everolimus-alone group, there was an objective response rate of 8.7%. In the combination group, the objective response rate was 26.8%. The disease control rate was 87% in the everolimus-alone group and 91.5% in the combination group. The study was stopped early because of improvement in progression-free survival in the combination group, so the everolimus/lanreotide combination could be offered to all participants.
There were more side effects in the drug combination treatment group. However, there was not a significant increase in severe side effects in this group.
Next Steps
The study authors concluded that patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors with poor prognostic factors and who receive treatment with a combination of everolimus/lanreotide may experience longer progression-free survival than with everolimus alone, with a manageable safety profile. Researchers plan to compare the everolimus/lanreotide combination therapy with other treatments for gastroenteropancreatic neuroendocrine tumors. Further, they noted the combination of everolimus/lanreotide may be a new standard treatment in the first-line setting for patients with well-differentiated grade 1 or 2 gastroenteropancreatic neuroendocrine tumors who have poor prognostic factors.
Expert Point of View
In a statement, ASCO Expert Laura Vater, MD, MPH, of Indiana University Simon Cancer Center in Indianapolis, shared these comments: “While lanreotide and everolimus have each previously demonstrated the ability to extend progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors, combination treatment of lanreotide with everolimus was previously unstudied. Establishing this new treatment option benefits patients by expanding their therapeutic choices and potentially improving their prognosis and quality of life.”
Disclosure: This study was funded by the National Cancer Center Research and Development Fund and the Japan Agency for Medical Research and Development. For full disclosures of all study authors, visit coi.asco.org.
