Economic impact and adverse effect analysis of everolimus with lanreotide in advanced gastroenteropancreatic neuroendocrine tumors: Implications from the STARTER-NET trial.

9 Background: In January 2025 data reported from the STARTER-NET trial (JCOG1901) demonstrated a significant progression-free survival (PFS) benefit with everolimus plus lanreotide (EV-LAN) versus everolimus (EV) alone in patients with non-functioning aggressive (Ki-67 5-20% or diffuse liver metastases) gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We analyzed the cost-effectiveness and adverse reactions (AEs) of this upfront combination treatment compared to monotherapy. Methods: We performed direct cost analysis using available U.S. drug pricing and AE management estimates. The median PFS from the STARTER-NET trial was used as a proxy for treatment duration. Incremental cost-effectiveness was estimated per month of PFS. Reported preliminary AEs from the STARTER-NET trial were compared to the EVELAR study to assess the estimates. Results: The total estimated cost of EV therapy is $177,500 over a median duration of 11.5 months. In comparison, the EV-LAN incurred a total cost of $698,100 over 29.7 months. The costs associated with managing adverse events were estimated at $5,000 for monotherapy and $15,000 for combination therapy. The incremental cost of PFS per additional month was approximately $28,555. No significant improvement in overall survival (OS) or quality of life was observed in the trial. Preliminary data on AEs from STARTER-NET reported diarrhea in 36.8% and mucositis in 62.1% of patients. The EVERLAR phase 2 study reported diarrhea in 70.9% and mucositis in 65.9 % of patients with EV-LAN. Interestingly STARTER-NET reported significantly higher hyperglycemia in 62.1% compared to 15.9 % in the EVERLAR study. Conclusions: Although EV-LAN showed significantly improved PFS in the STARTER-NET trial it incurs substantially higher costs with uncertain impact on quality-adjusted outcomes. The combination may not be cost-effective under typical willingness-to-pay thresholds, raising concerns about affordability and value, particularly lacking OS. These findings underscore the need to integrate cost analyses into treatment decision-making. Analysis of AEs confirms significantly lower diarrhea and higher occurrence of hyperglycemia compared to previous observations. The difference in side effect profile could be explained by patient demographics which also mandates confirmation of treatment response in patients with different demographics.