Are fosnetupitant (Netupitant) and fosaprepitant (Aprepitant) equally effective in preventing highly emetogenic chemotherapy-induced nausea and vomiting?

Fosnetupitant and Fosaprepitant Are Statistically Non-inferior for Preventing Chemotherapy-Induced Nausea and Vomiting

Based on the evidence from a randomized, double-blind phase III study, fosnetupitant is non-inferior to fosaprepitant for preventing highly emetogenic chemotherapy-induced nausea and vomiting, with a potential numerical advantage that does not reach statistical superiority. 1

Understanding the Trial Results

The CONSOLE trial directly compared these two NK1 receptor antagonists with the following key findings:

• Primary endpoint (overall complete response rate 0-120 hours):
  • Fosnetupitant: 75.2%
  • Fosaprepitant: 71.0%
  • Difference: 4.1% (95% CI, -2.1% to 10.3%) 1

The statistical interpretation of these results is important:

• The lower bound of the confidence interval (-2.1%) is greater than the prespecified non-inferiority margin (-10%), confirming non-inferiority 2
• However, since the confidence interval crosses zero (includes negative values), statistical superiority cannot be claimed 2

Clinical Implications

Both medications are NK1 receptor antagonists used as part of the recommended three-drug regimen for highly emetogenic chemotherapy:

• Current guidelines recommend an NK1 receptor antagonist (such as fosaprepitant or fosnetupitant) in combination with a 5-HT3 receptor antagonist and dexamethasone for preventing CINV in highly emetogenic chemotherapy 3

• Both agents are considered appropriate options within this class, with the choice potentially influenced by:

  • Safety profile: Fosnetupitant showed significantly fewer injection site reactions (11.0% vs. 20.6%, p<0.001) 1
  • Treatment-related adverse events were comparable (22.2% with fosnetupitant vs. 25.4% with fosaprepitant) 1

Extended Efficacy Analysis

Additional exploratory analyses showed consistent numerical advantages for fosnetupitant across multiple time periods:

• Extended overall phase (0-168 hours): 73.5% vs. 66.9% (p=0.0450) - statistically significant 4
• Beyond delayed phase (120-168 hours): 86.7% vs. 81.7% (p=0.0523) - approaching significance 4

Practical Considerations

When choosing between these agents, clinicians should consider:

1. Both medications are administered intravenously on day 1 only
2. Both are used as part of the standard three-drug regimen for highly emetogenic chemotherapy
3. Fosnetupitant may offer advantages in terms of reduced injection site reactions
4. The numerical advantage in efficacy for fosnetupitant may be clinically meaningful for some patients, even if not meeting statistical superiority criteria

Conclusion

From a statistical perspective, fosnetupitant and fosaprepitant should be considered equally effective based on the non-inferiority design and results of the CONSOLE trial. The confidence interval crossing zero means we cannot claim superiority, despite the numerical advantage observed with fosnetupitant. The choice between these agents should incorporate considerations of safety profile, particularly the lower incidence of injection site reactions with fosnetupitant.