Findings from the phase 3 STARTER-NET trial, presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, reveal that combining Afinitor (everolimus) with Somatuline (lanreotide) significantly extends progression-free survival (PFS) in patients with unresectable or recurrent gastroenteropancreatic neuroendocrine tumors (GEP-NETs) compared to Afinitor monotherapy. The study suggests a potential new first-line treatment option for this patient population, particularly those with aggressive tumors indicated by a high Ki-67 score.
Improved Progression-Free Survival
The interim analysis from the STARTER-NET trial, conducted in June 2024, demonstrated a median PFS of 29.7 months in the Afinitor plus Somatuline group, compared to 11.5 months in the Afinitor monotherapy group. This marked improvement highlights the synergistic effect of the combination therapy in delaying disease progression. The median overall survival (OS) analysis conducted in November 2024 was not evaluable (NE) in both groups. The one-year survival in the Afinitor plus Somatuline group was 96.2% compared to 97% in the Afinitor group.
The objective response rate (ORR) was also notably higher in the combination group, with 23% of patients experiencing tumor shrinkage compared to 8.3% in the Afinitor group. Specifically, 23% and 8.3% of patients, respectively, experienced partial responses (PRs), 69% and 76.2% had stable disease (SD), 2.3% and 10.7% had progressive disease, and 5.7% and 4.8% were NE. The disease control rate (DCR) was 92% and 84.5% respectively.
Safety and Tolerability
While the combination therapy demonstrated significant efficacy, it also presented a manageable safety profile. Grade 3 or worse side effects occurred in 35.6% of patients in the Afinitor and Somatuline group, compared to 14.9% in the Afinitor group. The most common side effects of any grade were oral mucositis (62.1% and 67.8%, respectively), hyperglycemia (62.1% and 33.3%) and diarrhea (36.8% and 26.4%). The most common side effects of grade 3 or worse were hyperglycemia (9.1% and 1.1%), oral mucositis (8.0% and 4.6%) and fatigue (5.7% and 1.1%).
Insights from Experts
Dr. Susumu Hijioka, from the Department of Hepatobiliary and Pancreatic Oncology at the National Cancer Center, emphasized the potential of the combination therapy, stating, "The combination of [Somatuline] and [Afinitor] significantly prolonged PFS in poor prognostic population of [grade 1 or 2 gastroenteropancreatic neuroendocrine tumors], with a manageable toxicity. Afinitor plus Somatuline has the potential to become a new standard first-line treatment for patients with unresectable or recurrent [gastroenteropancreatic neuroendocrine tumors] of poor prognostic population."
Dr. Laura Vater, assistant professor of clinical medicine at Indiana University Simon Cancer Center, highlighted the importance of expanding treatment options for patients with GEP-NETs. "While [Somatuline] and [Afinitor] have each previously demonstrated the ability to extend PFS in patients with gastroenteropancreatic neuroendocrine tumors, combination treatment of [Somatuline] with [Afinitor] was previously unstudied. Establishing this new treatment option benefits patients by expanding their therapeutic choices and potentially improving their prognosis and quality of life."
Study Design and Patient Population
The STARTER-NET trial randomly assigned 250 patients in a 1:1 ratio to either Afinitor at 10 milligrams per day plus Somatuline at 120 milligrams every 28 days, or Afinitor monotherapy at 10 milligrams per day. Subgroup analysis for PFS included patients with the first primary site of disease in the pancreas (118 patients) and the gastrointestinal tract (50 patients).
