New Hope for Difficult-to-Treat Childhood Cancers?
A clinical trial offers a potential roadmap for personalizing treatment in relapsed pediatric solid tumors.
A recent Phase I/II trial within the eSMART study has provided promising, if nuanced, results for children with relapsed solid tumors. The study investigated a combination therapy of low-dose irinotecan and a PARP inhibitor in 66 pediatric patients, including 36 with Ewing sarcoma and 34 with other tumor types.
The trial revealed that 12 patients experienced a significant benefit—either partial or complete tumor shrinkage, or stable disease lasting for more than six months.
"The study provides a potential roadmap for personalizing treatment in difficult-to-treat childhood cancers."
— Dr. Louise Hopkins
The Aneuploidy Connection
A key question for researchers was why some patients responded while others did not. Importantly, benefit from the therapy did not correlate with pre-specified gene alterations or a diagnosis of Ewing sarcoma.
However, a retrospective analysis uncovered a significant finding: patients with a high aneuploidy score in their tumors were significantly more likely to benefit from the treatment.
This suggests that the overall genomic instability of a cancer cell, rather than specific mutations, might be a crucial factor.
A Potential New Biomarker
- The trial was conducted across the UK, France, Netherlands, and Spain, sponsored by Gustave Roussy.
- All patients had relapsed multiple times, and cure was not expected at the time of enrollment.
- PARP inhibitors are already established in some adult cancers with specific DNA repair defects, but their potential in pediatric cancers is still under investigation.
High aneuploidy score may become a biomarker for DNA repair inhibitor trials in pediatric cancers, warranting further research.
— Dr. Susanne Gatz