Key result
Talazoparib in combination with irinotecan and radiation therapy resulted in a sustained complete response in a child with refractory BARD1-mutated neuroblastoma, remaining disease-free 22 months off therapy.
Why the study?
Does talazoparib combined with chemotherapy and radiation therapy improve clinical response in a child with BARD1-mutated refractory neuroblastoma?
Case Report (n=1)
No
Does talazoparib combined with chemotherapy and radiation therapy improve clinical response in a child with BARD1-mutated refractory neuroblastoma?
PARP inhibition combined with DNA-damaging agents may be effective in children with BARD1-mutated neuroblastoma, and adult HRD score thresholds may not be applicable in this population.
Suggests activity of PARP inhibition in BARD1-mutated neuroblastoma; hypothesis-generating and requires prospective validation before any practice consideration.
Despite advances in the treatment of high-risk neuroblastoma, approximately half of these patients die from the disease. Targeted therapy based on synthetic lethality associated with homologous recombination deficiency (HRD) caused by germline mutations in homologous recombination repair genes has shown great efficacy in several adult solid tumors. Here we report the first successful treatment of a pediatric patient with refractory neuroblastoma and a germline pathogenic mutation in BARD1 using a PARP inhibitor, talazoparib, in combination with cytotoxic chemotherapy and radiation therapy. Allele-specific expression in RNA-seq indicates bi-allelic loss of BARD1 in tumor; however, the HRD score was below the threshold currently used for HRD classification in adult cancers. Our study demonstrates that the use of PARP inhibition in combination with DNA-damaging agents should be considered in children with BARD1-mutated neuroblastoma and cautions against the use of HRD score alone as a biomarker for this pediatric population.
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Federico et al. (2023) conducted a case report in Refractory neuroblastoma with BARD1 germline pathogenic mutation (n=1). Talazoparib, irinotecan, and radiation therapy was evaluated on Clinical response (bone marrow disease status). Talazoparib in combination with irinotecan and radiation therapy resulted in a sustained complete response in a child with refractory BARD1-mutated neuroblastoma, remaining disease-free 22 months off therapy.
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