Novartis Receives FDA Approval for First-Ever Targeted Combination Therapy for Pediatric BRAF V600E Low-Grade Glioma
Novartis
Drug Development and Manufacturing
FDA
U.S. Food and Drug Administration
Novartis recently announced that the U.S. Food and Drug Administration (FDA) has approved the combination of dabrafenib and trametinib for the treatment of pediatric patients aged 1 year and older with BRAF V600E mutation-positive low-grade glioma (LGG) who require systemic therapy. The FDA also approved liquid formulations of dabrafenib and trametinib, marking the first time a BRAF/MEK inhibitor has been developed for use in patients as young as one year old.This approval makes dabrafenib and trametinib the first approved combination targeted therapy for the treatment of pediatric patients with BRAF V600E LGG.
Based on the results of the clinical trial TADPOLE, the overall response rate (ORR) for the dabrafenib and trametinib regimen was 47%, with a median progression-free survival (mPFS) of 20.1 months, while the ORR for the control group's standard treatment was 11%, with an mPFS of 7.4 months.1,2
Liquid formulations of dabrafenib and trametinib have also been approved to facilitate administration for various indications.
Dr. Eric Bouffet
Senior Research Associate at The Hospital for Sick Children, Toronto, Canada
Chief Investigator of the TADPOLE Clinical Trial
Pediatric oncology research is crucial for discovering new treatment methods, and developing targeted therapies based on the unique genetic characteristics of a patient's tumor is the future of pediatric cancer treatment.
LGG is the most common pediatric brain tumor. BRAFV600 mutations are present in 15-20% of pediatric LGGs and are associated with poor survival outcomes and a reduced response to chemotherapy.BRAF mutations have been identified as a driver of cancer growth in a variety of solid tumors and often have limited treatment options.3,4。
The FDA approval of dabrafenib in combination with trametinib is based on the results of the Phase 2 and Phase 3 clinical trial TADPOLE, which showed a statistically significant improvement in the overall response rate (ORR) among patients randomized to receive dabrafenib plus trametinib, with an ORR of 47% (CI: 35-59%), compared to 11% (CI: 3-25%) for those randomized to chemotherapy. After a median follow-up of 18.9 months, the median progression-free survival (PFS) was 20.1 months (CI: 12.8 months – not estimable) in the dabrafenib plus trametinib group, compared to 7.4 months (CI: 3.6-11.8 months, hazard ratio=0.31 (CI: 0.17-0.55, p<0.001)) in the chemotherapy group.
Dr. Roger Packer
National Children's Medical Center, USA
Senior Vice President of Neuroscience and Behavioral Medicine
Detecting gene mutations in patients with low-grade gliomas is more important than ever before. This FDA approval may offer new hope for pediatric patients with BRAF V600E mutant low-grade gliomas, potentially changing the way healthcare providers treat these pediatric patients and providing a significant advancement over chemotherapy.
ReshemaKemps-Polanco
Executive Vice President of Novartis US Oncology
The new indication for dabrafenib in combination with trametinib represents a potential new standard of care for young patients with BRAFV600E-mutated brain tumors, specifically designed for this population. We thank the families who participated in the clinical trials leading to this approval, as their bravery brings new hope to children suffering from this serious brain tumor.
Regarding the Dual-Target Treatment with Dabrafenib and Trametinib
Combination therapy with dabrafenib and trametinib slows tumor growth by blocking signaling associated with the BRAF and MEK kinases, which are related to the development of various cancers.1，2，3，4。
Reference
1.Mekinist[prescribinginformation].EastHanover,NJ:NovartisPharmaceuticalsCorp;2022.
2.Tafinlar[prescribinginformation].EastHanover,NJ:NovartisPharmaceuticalsCorp;2022.
3.TurskiML,etal.MolCancerTher.2016;15:533-547
4.PratilasC,etal.CurrTopMicrobiolImmunol.2012;355:82-98
Editor: Pea Shooter
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