The U.S. Food and Drug Administration (FDA) has granted approval to eflornithine (Iwilfin, US WorldMeds) for reducing the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB). This approval is specifically for patients who have achieved at least a partial response to prior multi-agent, multimodality therapy, including anti-GD2 immunotherapy. This marks the first FDA-approved therapy aimed at reducing relapse risk in pediatric HRNB patients.
The approval was based on data from an externally controlled trial (Study 3b, NCT02395666) that compared outcomes with a clinical trial-derived external control arm (Study ANBL0032). The FDA's decision highlights the potential of eflornithine in addressing the unmet need for therapies that can prevent relapse in this high-risk patient population.
Efficacy Data
Study 3b was a multi-center, prospective, open-label, non-randomized trial involving 105 eligible patients with HRNB. These patients received oral eflornithine twice daily, with the dosage adjusted based on body surface area (BSA), until disease progression, unacceptable toxicity, or up to two years. The primary endpoint was event-free survival (EFS), with overall survival (OS) as a secondary endpoint. The study compared these outcomes to historical EFS data from Study ANBL0032, which included 1241 patients in the experimental arm.
Eligible patients from Study 3b and ANBL0032 were matched in a 1:3 ratio using propensity scores. The matched efficacy populations for the primary analysis consisted of 90 patients treated with eflornithine and 270 control patients from Study ANBL0032.
The results showed a significant improvement in both EFS and OS. The hazard ratio (HR) for EFS was 0.48 (95% CI, 0.27-0.85), while the HR for OS was 0.32 (95% CI, 0.15-0.70). Supplementary analyses yielded EFS HRs ranging from 0.43 (95% CI, 0.23-0.79) to 0.59 (95% CI, 0.28-1.27) and OS HRs ranging from 0.29 (95% CI, 0.11-0.72) to 0.45 (95% CI, 0.21-0.98).
Safety Profile
The most common adverse effects observed in at least 5% of patients in Study 3b included otitis media, diarrhea, cough, sinusitis, pneumonia, upper respiratory tract infection, conjunctivitis, vomiting, pyrexia, allergic rhinitis, decreased neutrophils, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), hearing loss, skin infection, and urinary tract infection.
High-Risk Neuroblastoma Context
Neuroblastoma is the most common cancer in infants under one year old and the most frequent solid tumor outside the central nervous system in children. High-risk neuroblastoma accounts for approximately half of all neuroblastoma cases and is characterized by factors such as age, disease extent, histology, and cytogenetic features. Current treatment strategies involve intensive chemotherapy, radiation therapy, autologous stem cell transplant (ASCT), and immunotherapy. Despite advancements in treatment, HRNB remains a significant cause of pediatric cancer-related deaths.
Future Directions
Following the FDA approval, future research will likely focus on exploring eflornithine's efficacy in various neuroblastoma subtypes and its potential in combination with other therapies. Long-term monitoring of patients treated with eflornithine will be crucial to assess both efficacy and potential late side effects. Identifying biomarkers to predict patient response to eflornithine could further refine treatment strategies and improve outcomes.
