FDA approves Iwilfin for high-risk neuroblastoma
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The FDA approved eflornithine for adults and children with high-risk neuroblastoma.
The approval — the first for a therapy to reduce risk for relapse among children with high-risk neuroblastoma — applies to use of the agent by patients who achieved at least a partial response to previous multiagent, multimodality therapy, including anti-GD2 immunotherapy.
Eflornithine (Iwilfin, USWM LLC) is a specific, irreversible inhibitor of the enzyme ornithine decarboxylase.
The FDA based approval on results of an externally controlled trial that compared outcomes from two studies.
The control arm consisted of 1,241 patients from the experimental arm of Study ANBL0032, a randomized multicenter trial that compared dinutuximab, granulocyte-macrophage colony-stimulating factor, interleukin-2 and cis-retinoic vs. cis-retinoic acid alone for children with high-risk neuroblastoma.
The investigational arm included patients from Study 3b, a prospectively designed open label, nonrandomized trial that served as a comparator for historical benchmark EFS from ANBL0032.
The Study 3B analysis included 105 eligible patients with high-risk neuroblastoma who received oral eflornithine twice daily at doses based on body surface area. Treatment continued for 2 years, or until disease progression or unacceptable toxicity.
Researchers matched eligible patients from ANBL0032 and Study 3b in a 3:1 ratio using propensity scores, with the primary analysis including 270 patients from Study ANBL0032 and 90 treated with eflornithine.
Results showed a statistically significant improvement in EFS — the major efficacy outcome — with eflornithine (HR = 0.48; 95% CI, 0.27-0.85).
Results also showed improved OS in the eflornithine group (HR = 0.32; 95% CI, 0.15-0.7).
Due to the uncertainty of treatment effect estimation because of the externally controlled study design, researchers performed supplementary analyses in subpopulations or using other statistical methods.
Results of these analyses showed HRs for EFS ranging from 0.43 (95% CI; 0.23-0.79) to 0.59 (95% CI; 0.28-1.27), and HRs for OS ranging from 0.29 (95% CI; 0.11-0.72) to 0.45 (95% CI; 0.21-0.98).
The most common adverse reactions reported in Study 3b included otitis media, diarrhea, cough, sinusitis, pneumonia, upper respiratory tract infection, conjunctivitis, vomiting, pyrexia, allergic rhinitis, decreased neutrophils, increased alanine aminotransferase or aspartate aminotransferase, hearing loss, skin infection and urinary tract infection.
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