On December 13, 2023, the Food and Drug Administration (FDA) achieved a significant breakthrough by granting approval to eflornithine (IWILFIN, USWM, LLC) for use in both adult and pediatric patients facing the challenges of high-risk neuroblastoma (HRNB). This groundbreaking decision marks the first-ever FDA approval of a therapy designed to reduce the risk of relapse specifically in pediatric patients with HRNB.
Understanding the Approval and Efficacy of Eflornithine
The FDA’s approval was based on a comprehensive evaluation of eflornithine’s efficacy in an externally controlled trial. This trial compared outcomes from Study 3b (investigational arm) and Study ANBL0032 (clinical trial-derived external control arm).
Study Design and Patient Cohorts
Study 3b (NCT02395666) involved 105 eligible patients with HRNB from one cohort (Stratum 1), receiving eflornithine orally twice daily based on body surface area (BSA). The study aimed to compare outcomes with the historical benchmark event-free survival (EFS) rate from Study ANBL0032, a randomized trial of dinutuximab, granulocyte-macrophage colony-stimulating factor, interleukin-2, and cis-retinoic acid compared to cis-retinoic acid alone in pediatric patients with HRNB.
Key Efficacy Measures
The primary efficacy outcome measure was event-free survival (EFS), encompassing disease progression, relapse, secondary cancer, or death due to any cause. Additional efficacy measures included overall survival (OS), defined as death due to any cause.
In the protocol-specified primary analysis, the EFS hazard ratio (HR) was 0.48 (95% CI: 0.27, 0.85), and OS HR was 0.32 (95% CI: 0.15, 0.70). Supplementary analyses showed variations in HR, emphasizing the need for a comprehensive understanding of treatment effects.
Response Rate and Disease Control Rate:
Beyond survival measures, it’s crucial to understand the treatment’s impact on the disease. The response rate, indicating the proportion of patients showing a significant reduction in tumor size, was notable in patients treated with eflornithine. Additionally, the disease control rate, which includes patients with stable disease, showed encouraging results.
Safety Profile and Adverse Reactions
Eflornithine demonstrated a generally manageable safety profile. The most common adverse reactions (≥5%) in Study 3b included otitis media, diarrhea, cough, sinusitis, pneumonia, upper respiratory tract infection, conjunctivitis, vomiting, pyrexia, allergic rhinitis, decreased neutrophils, increased ALT, increased AST, hearing loss, skin infection, and urinary tract infection.
Dosage and Recommendations
The recommended dose is based on BSA. Healthcare providers are encouraged to refer to the prescribing information for comprehensive details on dosage and administration.
Expedited FDA Programs and Reporting
This review utilized the Real-Time Oncology Review (RTOR) pilot program, expediting data submission. The application was granted priority review, breakthrough designation, and orphan drug designation. Healthcare professionals are urged to report any adverse events associated with eflornithine to the FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Stay Informed and Engage
To stay updated on crucial developments in oncology and pediatric care, subscribe to our newsletter for the latest updates. Follow MedOnCmd on social media networks, @FDAOncology, for real-time updates and valuable insights.
Remember, healthcare professionals play a vital role in advancing patient care. Together, we can make strides in the fight against high-risk neuroblastoma.
At MedOncMD, a diverse array of valuable information is at your disposal, covering various aspects of cancer care, raising awareness, strategies for prevention, sustaining a healthy lifestyle, and staying updated with the latest research developments. Join our Cancer Support and awareness group!
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.
Embrace the opportunity to engage with Dr. Sajeve’s expertise, and feel empowered to explore the vast expanse of oncology with renewed curiosity and understanding on “Ask MedOnCMD“