A New Approach To Childhood Neuroblastoma

(Posted on Friday, March 7, 2025)

Childhood neuroblastoma is often a fatal disease. Despite initial treatment success, most patients relapse or develop resistance to the current therapies. A new approach using a combination of two drugs shows promise in reducing relapse rates and improving long-term survival.

Combination Therapy: A Proven Strategy

The current treatment for neuroblastoma relies on topoisomerase inhibitors, which disrupt DNA replication. While these drugs can induce remission, long-term survival rate remains unfavorable.

A new approach involves a two drug combination that adds a monoclonal antibody to traditional treatment. The monoclonal antibody, bevacizumab (B), inhibits blood vessel formation. Tumors rely on new blood supplies to grow, and blocking key growth factors required for blood vessel formation can improve outcomes. In this study, topoisomerase inhibitor-based therapy was combined with a monoclonal antibody targeting vascular endothelial growth factor. The antibody, bevacizumab (B), is used for the treatment of other cancers and for treatment of macular degeneration.

The BEACON Mission: A Smarter Way to Test Treatments

An innovative trial design enabled the evaluation of multiple treatment combinations. A total of 160 children with neuroblastoma were enrolled and evenly divided into four groups of 40. Each group received different combinations of topoisomerase inhibitors—irinotecan and temozolomide—with or without the monoclonal antibody bevacizumab. This approach allowed researchers to identify the most effective strategies for treating relapsed or refractory neuroblastoma. Additionally, the design facilitated direct comparisons between treatment arms and how the antibody contributed to overall efficacy.

Combinational Drug Shows Promising Results

The combination of two drugs was superior to using the single drug alone. Children receiving the combination therapy bevacizumab, irinotecan, and temozolomide had a 33 percent response rate as opposed to 18 percent of the standard therapy. The trial showed using combination with antibody also improved long-term survival rate of 54 percent compared to 33 percent.

Irinotecan and Bevacizumab: A Powerful Cancer-Fighting Pair?

There was one other benefit. The combination had better results than anticipated. The interaction between irinotecan and bevacizumab showed a p-value of 0.11, indicating significance. One possible explanation is that monoclonal antibody encourage the presence of tumor-fighting lymphocytes, adding an extra layer of potency.

By design, the two drug combinations may create a “hostile” environment for the neuroblastoma cells. Antibody bevacizumab blocks vascular endothelial growth factor (VEGF), a protein essential for blood vessel formation. By cutting off this supply, bevacizumab essentially “starves” the tumor, enhancing irinotecan’s ability to penetrate cancer cells. It also disrupts the tumor’s ability to repair DNA damage caused by chemotherapy, making irinotecan more effective. Together, these drugs reshape the immune response, leaving the tumor more vulnerable. Yet, the exact mechanisms behind how the two drugs interact remain unclear.

Although the two drug combinations have better results than the single drug alone, there is room for further improvements. The final results were that the combination improved response rates by 15 percent and long term survival rate by 21 percent. From this study, it is clear that using combination therapy is better than a single drug alone. Perhaps a three-drug regimen incorporating antibodies from a different drug class may be even more effective in getting higher response rates and dramatic increases in long term survival.

For children and families battling neuroblastoma, the BEACON-Neuroblastoma trial offers a hopeful outlook. This trial lays the groundwork for further testing, which could lead to even more positive results and improved long-term survival.