A New Era of Precision Medicine for Childhood Cancer

Childhood cancers are rare, but for the families facing them, they are devastating, scary and challenging to navigate. In many cases, the genomic drivers of pediatric tumors are completely distinct to those of adults, which can potentially translate into better treatment outcomes.¹ For example, pediatric tumors are often driven by one or two spontaneous mutations, whereas adult tumors can have hundreds of driver mutations.¹

These differences can have significant implications for treatment in pediatric cancers, because fewer mutations mean that targeted treatments can have greater efficacy.¹ Despite this potential, the rarity of pediatric cancers has traditionally been a barrier to research. 

The unmet need in pediatric low-grade glioma

For patients with pediatric low-grade glioma (pLGG), progress is now being made at a rapid pace. pLGG is the most common form of childhood brain tumor, accounting for approximately 30% of all childhood central nervous system (CNS) tumors.² Although pLGG tumors are generally slow-growing with high survival rates, they are associated with significant tumor and treatment-related morbidities that can lead to lifelong ill health and disability.² Tumor growth – and the toxicity associated with treatment – can have devastating effects on the brain, leading to ocular/visual damage, mental health disorders, seizures and behavioral or cognitive disorders.²

The mainstay of treatment for pLGG is surgical resection, but where this is not possible, radiation and chemotherapy have been the traditional standard of care. Over the past decade, we have gained important insights into the genomic landscape of pLGG.³ Research confirms that these tumors are distinct from low-grade gliomas that occur in adults, and that the genomic drivers of pLGG, such as BRAF alterations, result in activation of the mitogen-activated protein kinase (MAPK) pathway.³ 

Understanding the full landscape of genomic alterations in pLGG

Alterations in the BRAF gene can drive tumor proliferation in pLGGs and are detected in up to 75% of cases.^3,4 BRAF V600E is the most common BRAF mutation, which occurs in around 17% of pLGGs and responds well to first-generation BRAF inhibitors.³

Fusions in the BRAF gene are also common. However, for patients with BRAF fusions as opposed to BRAF mutations, first-generation BRAF inhibitors are not indicated for treatment as they can lead to accelerated disease progression.³ The introduction of next-generation BRAF inhibitors offers new targeted treatment options for patients with both BRAF fusions and BRAF mutations. The hope is that these new treatments will offer improved tumor control and fewer side effects compared to chemotherapy, and that this will result in reduced long-term morbidity.

An unmet need for comprehensive BRAF testing

Determining the nature of the BRAF alteration is therefore critical before initiating treatment, but not all standard genomic tests can detect BRAF fusions. FoundationOne®CDx⁵ is now approved by the U.S. Food and Drug Administration (FDA) for use as a companion diagnostic for a targeted therapy to treat patients six months of age and older with relapsed or refractory pLGG harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.⁶

FoundationOne®CDx is able to detect both BRAF V600 mutations and fusions.⁵ This enables healthcare providers to gain a more complete genomic picture of their patient’s tumor through a single test, ensuring more patients can benefit from treatment decision-making based on high-quality information.

A more personalized future for treating pediatric cancer

We are hopeful that this important approval is the first of many and that it signals the arrival of a new era of precision medicine in childhood cancer that will bring hope to the thousands of children diagnosed each year.