Tumor Lineage–Specific Disparities in Access to Genome-Matched Therapies Among Adolescents and Young Adults in Japan: A Nationwide Genomic Profiling Study

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Abstract
PURPOSE: Adolescents and young adults (AYAs) with cancer are a biologically heterogeneous population with both pediatric- and adult-type malignancies. Tumor lineage rather than patient age often determines genomic architecture and therapeutic targetability, and understanding lineage-specific differences is essential to evaluate the clinical utility of comprehensive genomic profiling (CGP) in this population. This study aimed to compare genomic alterations and access to genome-matched therapies between pediatric-type and adult-type tumors among AYAs in Japan, using nationwide CGP data. PATIENTS AND METHODS: We analyzed data from 2,325 AYAs with cancer who underwent CGP in a routine clinical practice in Japan. Tumors were classified as pediatric or adult type using established tumor lineage frameworks. Genomic alterations were annotated using OncoKB, and the prevalence of pathogenic variants, actionable alterations, and genome-matched therapies was evaluated at the patient level. RESULTS: Among 2,325 AYAs, 35.4% had pediatric-type and 64.6% had adult-type tumors. At least one pathogenic genomic alteration was identified in 67.8% of pediatric-type tumors and 76.3% of adult-type tumors with actionable alterations detected in 49.4% and 59.6%, respectively. Access to genome-matched therapies differed substantially between the two groups, with markedly lower treatment rates in pediatric-type tumors than in adult-type tumors (2.9% v 9.7%). This disparity reflects both differences in the genomic landscapes of pediatric- and adult-type tumors and historical limitations in drug availability in Japan. CONCLUSION: Overall access to genome-matched therapies among AYAs with tumors in Japan was comparable with that reported for the general cancer population, but there are substantial lineage-specific disparities. Patients with pediatric-type tumors remain underserved, highlighting a genome-to-therapy gap driven by both tumor lineage–specific differences in therapeutic targetability and regulatory constraints.

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