NEW findings demonstrate that the integration of precision genomic testing (PGT) with targeted anti-cancer therapies in paediatric oncology is associated with improved treatment responses and progression free survival. Thus, demonstrating improved treatment outcomes can be achieved by tailoring therapy to individual genetic profiles. Despite successful identification of molecular targets in over 65% of high-risk pediatric cancer cases, clinical adoption of PGT remains limited, primarily due to uncertainties among physicians regarding its efficacy and risk-benefit balance.
Addressing this gap, the Australian ZERO Childhood Cancer Precision Medicine Program conducted a multicenter cohort-based clinical trial involving 384 pediatric patients with suspected or confirmed high-risk malignancies. Spanning from September 2017 to June 2022, the study aimed to assess the clinical relevance and outcomes of PGT recommendations made within a comprehensive molecular tumor board framework.Participants, aged under 21 years, underwent whole genome sequencing of paired tumor-germline DNA samples, alongside DNA methylation analysis. Weekly molecular tumor board meetings convened experts to review each patient’s genomic data, facilitating informed decisions on PGT recommendations.
Results revealed that of the cohort, 67% were advised for PGT, marking a notably high uptake in pediatric oncology studies. Among those recommended, 110 patients received PGT, demonstrating a 36% objective response rate and a 26% two-year progression-free survival (PFS) rate, compared to lower rates with standard care or targeted agents. Importantly, PGT significantly outperformed unguided therapy, underscoring the critical role of molecular evidence in therapeutic decision-making. While PGT showed substantial benefits in terms of PFS, the study did not find significant differences in overall survival at two years, emphasizing the need for longer follow-up studies. Nonetheless, the findings underscore the clinical utility of PGT in enhancing treatment responses and PFS outcomes in pediatric oncology.
The study’s insights highlight the significance of integrating genomic biomarkers into standard of care for pediatric cancer patients, paving the way for personalized therapeutic strategies. Researchers concluded that moving forward, optimizing combination therapies and refining the timing of PGT interventions will be pivotal in further improving outcomes for this vulnerable patient population.
Reference:
Lau, L. M. S. et al. Precision-guided treatment in high-risk pediatric cancers. Nat Med 2024;1-10.
