The FDA has approved eflornithine (Iwilfin), marking a significant milestone in treating high-risk neuroblastoma (HRNB). This groundbreaking decision paves the way for enhanced relapse prevention in both adult and pediatric patients who have exhibited partial responses to previous multi-agent and multimodality treatments, including anti-GD2 immunotherapy.
The approval of eflornithine (Iwilfin) by the FDA is a historic moment, representing the first-ever therapy indicated for reducing the risk of relapse specifically in pediatric patients with high-risk neuroblastoma. This development offers newfound hope and optimism to children and their families who have faced the challenges posed by this high-risk form of neuroblastoma.
Robust Clinical Evidence in Neuroblastoma Relapse Treatment Evaluation
This landmark decision by the FDA is backed by robust clinical evidence from an externally controlled trial that meticulously evaluated data from two critical studies: Study 3b (NCT02395666) and Study ANBL0032. The comprehensive analysis encompassed investigational and clinical trial-derived external control cohorts.
Study 3b, a multi-center, prospective, open-label trial, enrolled 105 eligible patients with HRNB. These patients were administered oral eflornithine twice daily, with dosages adjusted according to their body surface area (BSA). Treatment continued until disease progression and unacceptable toxicity occurred or for up to two years. This study served as the foundation for the evaluation of historical benchmark event-free survival (EFS) data gathered from Study ANBL0032.
Study ANBL0032, a multi-center, open-label, randomized trial, focused on pediatric patients with HRNB. It compared the efficacy of dinutuximab, granulocyte-macrophage colony-stimulating factor, interleukin-2, and cis-retinoic acid against cis-retinoic acid alone. The external control cohort included 1241 patients from the experimental arm of Study ANBL0032.
To ensure the integrity of the comparative analysis between Study 3b and ANBL0032, eligible patients were meticulously matched using propensity scores at a 1:3 ratio. The matched efficacy populations formed the basis for the primary analysis, involving 90 patients administered Iwilfin and 270 patients from the control cohort of Study ANBL0032. The primary endpoint of the trial was event-free survival (EFS), with overall survival (OS) as a secondary endpoint.
The protocol-specified primary analysis yielded compelling results, with an EFS hazard ratio (HR) of 0.48 (95% CI, 0.27-0.85) and an OS HR of 0.32 (95% CI, 0.15-0.70). Supplementary analyses for subpopulations and alternative statistical methods were conducted due to the externally controlled study design, affirming the efficacy of Iwilfin. The range for EFS HR spanned from 0.43 (95% CI, 0.23-0.79) to 0.59 (95% CI, 0.28-1.27), while the OS HR range extended from 0.29 (95% CI, 0.11-0.72) to 0.45 (95% CI, 0.21-0.98).
Milestone in High-Risk Neuroblastoma Treatment with a Focus on Safety
As for safety, the most commonly reported adverse effects in Study 3b included otitis media, diarrhea, cough, sinusitis, pneumonia, upper respiratory tract infection, conjunctivitis, vomiting, pyrexia, allergic rhinitis, decreased neutrophils, increased alanine aminotransferase, increased aspartate transaminase, hearing loss, skin infection, and urinary tract infection.
This landmark FDA approval reflects a monumental stride in the treatment of high-risk neuroblastoma. It reaffirms the commitment to advancing therapies that can significantly reduce the risk of relapse and improve the prognosis for pediatric patients facing the challenges of HRNB.
Resource: Pharmexec, December 14, 2023
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