Early Success of Targeted Therapy in Treating High-Quality Pediatric Gliomas

Hope Emerges: Targeted Therapy Shows Promise for Pediatric Brain Cancer

Avapritinib offers a new avenue for treating high-grade gliomas in children, showing potential for clinical improvement. Clinical trials are underway too confirm efficacy.

March 21, 2025

A Glimmer of Hope for Pediatric Brain Cancer

in a significant stride, a team of international clinical collaborators, spearheaded by researchers at the dana-Farber Cancer Institute, has reported encouraging initial results from a clinical trial evaluating Avapritinib as a targeted therapy for pediatric and young adult patients battling high-grade gliomas. The preliminary findings suggest that Avapritinib, already sanctioned by the FDA for specific adult cancers, exhibits a promising safety profile and demonstrates the potential to reduce tumor size, alongside tangible clinical improvements, in a subset of patients.

High-grade gliomas represent a particularly devastating form of pediatric brain cancer. The current standard treatments, involving surgery and radiation, often fail to provide long-term solutions, with median survival times lingering below 18 months post-diagnosis. This grim reality underscores the critical need for innovative therapeutic strategies.

The study, published in Cancer cell, details how Avapritinib, a small molecule designed to navigate the blood-brain barrier, targets a specific abnormality: hyperactivity of the Growth factor derived from alpha plates (PDGFRA) pathway. This pathway is implicated in the uncontrolled proliferation of cancer cells in certain high-grade pediatric gliomas. Recognizing the potential of these findings, the research team is now designing an expanded clinical trial to assess the efficacy of Avapritinib in a larger cohort of newly diagnosed pediatric patients with PDGFRA-driven high-grade gliomas.

Avapritinib: A Targeted Approach

Avapritinib represents a significant advancement in targeted cancer therapy. Unlike customary chemotherapy, which indiscriminately attacks rapidly dividing cells (both cancerous and healthy), Avapritinib is engineered to selectively inhibit the activity of PDGFRA. This precision targeting aims to minimize off-target effects and reduce the debilitating side effects frequently enough associated with conventional cancer treatments.

“In a very aggressive disease with no effective targeted treatment options currently available, we were delighted to observe a radiographic and clinical response in a subset of very relieved and highly refractory patients after monotherapy with a small molecule inhibitor,” said Mariella Filbin, MD, PHD, principal author, president of Jan Paradise in Brain Cancer Research.

Dr. Filbin’s team had previously identified that alterations in the PDGFRA gene are present in approximately 15% of pediatric high-grade glioma cases,contributing to the aggressive nature of the disease. This discovery laid the groundwork for exploring Avapritinib as a potential therapeutic intervention.

Challenges and Breakthroughs in Targeting PDGFRA

Past attempts to target PDGFRA in high-grade gliomas have been largely unsuccessful. This is likely due to limitations in the pharmacokinetic properties of earlier drugs, preventing them from effectively reaching and inhibiting the target within the brain. Avapritinib, however, represents a new generation of PDGFRA inhibitors, engineered for enhanced selectivity and brain penetration. Preclinical studies conducted by Dr. Filbin’s team demonstrated that Avapritinib effectively reduced tumor growth in both cell-based and animal models of PDGFRA-driven gliomas. These promising preclinical results prompted the team to collaborate with clinical partners at the University of Michigan and the Medical University of Vienna to offer Avapritinib to a small group of patients with recurrent PDGFRA-mutant high-grade gliomas through a compassionate use program.

“It was really inspiring to see how our scientific research could be quickly translated into clinical practice, benefiting directly to patients,” explains Sina Neyazi, MD, postdoctoral scholarship holder of Filbin Lab. “This discovery was made possible by the dedication of our clinical employees and the immense confidence of patients and their families.”

Future Directions and Personalized Treatment Strategies

Looking ahead, Dr. Filbin’s team plans to investigate whether specific genetic alterations within the tumors can predict a patient’s response to Avapritinib, paving the way for personalized treatment strategies. Additionally,they are exploring the potential of combining Avapritinib with other FDA-approved drugs to maximize therapeutic efficacy and circumvent the development of treatment resistance.

The development of resistance to targeted therapies is a common challenge in cancer treatment. Cancer cells are adept at evolving and finding choice pathways to bypass the effects of the drug. Therefore, combination therapies that target multiple vulnerabilities within the cancer cell are often more effective at achieving durable responses.

“As a doctor, it is indeed heartbreaking to tell a family that their child’s tumor returned despite the treatment standard,” explains Filbin. “Our latest discoveries with the cerebral penetrating PDGFRA The Avapritinib inhibitor is encouraging for a subset of our patients who have genetic alterations in the CEO, and I hope that this will open the way to developing innovative combined treatments that include avepritinib.”

Implications for U.S. Patients and Families

the potential impact of Avapritinib on pediatric brain cancer treatment in the United States is significant. high-grade gliomas represent a major cause of cancer-related mortality in children and adolescents. The development of a targeted therapy that can effectively control tumor growth and improve clinical outcomes would offer a much-needed advancement for these patients and their families.

For U.S.families facing this diagnosis, the availability of clinical trials evaluating Avapritinib is paramount. These trials provide access to cutting-edge treatments and contribute to the advancement of scientific knowledge. Families can explore clinical trial options through resources such as the National Cancer Institute (NCI) and the Children’s Oncology Group (COG).

The FDA approval of Avapritinib for certain adult cancers provides a pathway for potential accelerated approval for pediatric indications if the ongoing clinical trials demonstrate sufficient efficacy and safety. The FDA’s Breakthrough Therapy designation can expedite the development and review of drugs that show promise in treating serious or life-threatening conditions.

Understanding High-Grade Gliomas: Key Facts

Fact	Details
Type of Cancer	Aggressive brain tumor
Patient Group	Primarily affects children and adolescents
Current treatment	Surgery and radiation
Survival Rate	Median survival less than 18 months post-diagnosis
Innovations	Avapritinib targets specific gene mutations

Addressing Potential Concerns

While the initial findings are promising, it’s crucial to acknowledge potential limitations and address counterarguments. The initial clinical trial involved a small number of patients, and the observed responses were not worldwide. Further research is needed to confirm the efficacy and safety of Avapritinib in a larger and more diverse patient population.

Additionally, the long-term effects of Avapritinib treatment in children are not yet fully understood. Careful monitoring and follow-up will be essential to assess for any potential late-onset toxicities.

The cost of targeted therapies can also be a concern for many families. Access to Avapritinib, if approved, will need to be ensured through appropriate insurance coverage and patient assistance programs.

What are the potential long-term effects of Avapritinib that researchers and families should be aware of?

Targeted Therapy Breakthrough: Interview with Dr. Evelyn Reed on Pediatric Glioma Treatment

Introduction

Welcome to Archyde News. Today, we have Dr. Evelyn Reed, a leading pediatric oncologist at the National Children’s Cancer Centre, to discuss the promising results surrounding the use of Avapritinib in treating high-grade gliomas in children.Dr. Reed,thank you for joining us.

Understanding the Challenge

Archyde News: Dr. Reed, high-grade gliomas are notoriously tough to treat, especially in young patients. Can you give us an overview of why these tumors are so challenging?

Dr.Reed: Certainly. High-grade gliomas are aggressive brain tumors that regrettably have a devastating impact on pediatric patients. Current treatments, such as surgery and radiation, often have limitations, and the survival rates have remained stubbornly low, usually under 18 months after diagnosis. This reality highlights the urgent need for new, more effective treatment strategies.

Targeted Approach with Avapritinib

Archyde News: This is where Avapritinib comes in. Can you explain how Avapritinib differs from customary chemotherapy and how it targets these tumors?

Dr. Reed: Avapritinib is a targeted therapy. Unlike chemotherapy, which attacks rapidly dividing cells, Avapritinib specifically targets the PDGFRA pathway, which, when overactive, drives the growth of certain glioma cells. This targeted approach aims to minimize side effects and improve treatment outcomes.

Initial Clinical Trial Findings

Archyde News: The initial results appear promising.What were the key findings from the initial clinical trials, and what do they suggest?

Dr. Reed: absolutely, the initial findings we have seen are exciting. Some patients who have a specific genetic alteration in their tumors, and who have high-grade gliomas with PDGFRA abnormalities have responded well to Avapritinib, with some experiencing a reduction in tumor size and clinical improvements too. This is a very vital first step in helping patients.

Looking Ahead: Personalized Treatment and Combination Therapies

Archyde News: What are the next steps in the research, Dr. Reed? What future treatment strategies are being explored?

Dr. Reed: We will be expanding clinical trials to assess Avapritinib in a broader patient population. We are also exploring personalized treatment approaches. We will be investigating specific genetic changes associated with responses to Avapritinib. Additionally, we’re excited about how we can test combination therapies.

Patient Impact and Access to Trials

Archyde News: What would you say to families in the U.S. who are facing this diagnosis? Is Avapritinib already available, and how can they access it?

Dr. Reed: I will be advising families that they should definitely discuss the available clinical trials of Avapritinib. These trials are critical, and can be accessed through resources such as the National Cancer Institute (NCI) and the Children’s Oncology Group (COG).Some patients are already being helped, and the FDA has provided mechanisms for the process to be accelerated.

Addressing Concerns and Future Research

Archyde News: What are some concerns that researchers and families need to take into consideration? What future research is important?

dr. Reed: Potential long-term effects of Avapritinib must be continuously monitored. Costs are also a potential concern. Further research must focus on the effectiveness of the drug in diverse patient populations. We are working hard to make it available.

Concluding Thoughts

Archyde News: Dr. Reed, this is very encouraging news. What is the most important take-away that you want to share with our readers?

Dr. Reed: The use of Avapritinib marks a turning point in pediatric brain cancer treatment, which may usher in personalized treatment and improved outcomes for children. This is a beacon of hope, and it shows the importance of dedicated research programs.

Reader Engagement

Archyde News: Thank you, Dr. Reed, for sharing your insights. This progress is indeed a significant step forward. Readers, what are your thoughts on this possibly groundbreaking therapy? Share your comments below.