STARTER-NET

Last year, results of the phase III STARTER-NET trial showed that adding lanreotide to everolimus significantly improves the progression-free survival (PFS) of patients with unresectable or recurrent gastro-enteropancreatic neuroendocrine tumors (GEP-NETs) (grade 1/2). In this video, Prof Dr Ivan Borbath, digestive oncologist at the Cliniques Universitaires Saint-Luc in Brussels discusses subgroup data of this trial presented during the 2025 annual ENETS meeting in Krakow.

STARTER-NET is a Japanese, randomized, phase III trial in which 250 patients with grade 1/2 GEP-NET who did not yet receive treatment for metastatic or recurrent disease were randomly assigned to receive everolimus alone (10mg/day) or in combination with lanreotide (120mg every 28 days). To be eligible for the study patients had to have an ECOG performance status of 0-2, be 20 years or older and have a Ki-67 index of 5-20%, of <5% in combination with diffuse liver metastases. The primary endpoint of the trial was PFS, with overall survival (OS), overall response rate (ORR), disease control rate (DCR) and safety as secondary objectives.

The median age of patients in the study was 62 years and about 70% had the pancreas as primary tumor location. Updated PFS results indicate a median of 13.6 months for everolimus monotherapy as compared to 29.7 months with the everolimus-lanreotide combination (HR[95%CI]: 0.44[0.28-0.69]; p= 0.00016). The benefit in PFS was observed, irrespective of age (<65 vs. ≥65 years), sex, primary tumor site (pancreas vs. GI tract) and Ki-67 proliferation index. For the moment, there is no difference in OS between the two treatment arms (1-year OS rate: 97.0% vs. 96.2% for everolimus and everolimus-lanreotide, respectively). 

Interestingly, the study demonstrated an ORR of 23% with the combination of everolimus and lanreotide, which is markedly better than what can be obtained with lanreotide or everolimus alone (8.3%). Subgroup data for ORR, presented at ENETS 2025, confirm this benefit in ORR across all the investigated subgroups, with the highest ORR for everolimus-lanreotide in patients younger than 65 years (28.0%), in female patients (25.5%), in patients with a pancreatic primary (26.2%) and in patients with a higher Ki-67 index (24.3% and 29.6% in patients with a Ki-67 index between 5 and 10% and above 10%, respectively).

In conclusion, these STARTER-NET data confirm the previously reported benefit in PFS and ORR obtained with the addition of lanreotide to everolimus across the different investigated subgroups. As such, these data identify lanreotide-everolimus as a potential first line treatment option for grade 1/2 GEP-NET patients with a poor prognosis.