Addressing the knowledge gap in the genomic landscape and tailored therapeutic approaches to adolescent and young adult cancers

•Comprehensive genomic profiling of AYA patients with cancer was conducted.•Genomic status, genome-matched therapies, and overall survival were compared with OA patients with cancer.•AYA patients had higher rates of BRCA1 and MYC alterations than older patients.•Genome-matched therapy use was similar between groups, with overall survival tending to improve in both.•There was some suggestion of the benefits of receiving drugs guided by comprehensive genomic profiling in both groups. BackgroundAdolescents and young adults (AYAs) represent a small proportion of patients with cancer. The genomic profiles of AYA patients with cancer are not well-studied, and outcomes of genome-matched therapies remain largely unknown.Patients and methodsWe investigated differences between Japanese AYA and older adult (OA) patients in genomic alterations, therapeutic evidence levels, and genome-matched therapy usage by cancer type. We also assessed treatment outcomes.ResultsAYA patients accounted for 8.3% of 876 cases. Microsatellite instability-high and/or tumor mutation burden was less common in AYA patients (1.4% versus 7.7% in OA; P = 0.05). However, BRCA1 alterations were more common in AYA patients with breast cancer (27.3% versus 1.7% in OA; P = 0.01), as were MYC alterations in AYA patients with colorectal cancer (23.5% versus 5.8% in OA; P = 0.02) and sarcoma (31.3% versus 3.4% in OA; P = 0.01). Genome-matched therapy use was similar between groups, with overall survival tending to improve in both. However, in AYA patients, the small number of patients prevented statistical significance. Comprehensive genomic profiling-guided genome-matched therapy yielded encouraging results, with progression-free survival of 9.0 months in AYA versus 3.7 months in OA patients (P = 0.59).ConclusionOur study suggests that tailored therapeutic approaches can benefit cancer patients regardless of age. Adolescents and young adults (AYAs) represent a small proportion of patients with cancer. The genomic profiles of AYA patients with cancer are not well-studied, and outcomes of genome-matched therapies remain largely unknown. We investigated differences between Japanese AYA and older adult (OA) patients in genomic alterations, therapeutic evidence levels, and genome-matched therapy usage by cancer type. We also assessed treatment outcomes. AYA patients accounted for 8.3% of 876 cases. Microsatellite instability-high and/or tumor mutation burden was less common in AYA patients (1.4% versus 7.7% in OA; P = 0.05). However, BRCA1 alterations were more common in AYA patients with breast cancer (27.3% versus 1.7% in OA; P = 0.01), as were MYC alterations in AYA patients with colorectal cancer (23.5% versus 5.8% in OA; P = 0.02) and sarcoma (31.3% versus 3.4% in OA; P = 0.01). Genome-matched therapy use was similar between groups, with overall survival tending to improve in both. However, in AYA patients, the small number of patients prevented statistical significance. Comprehensive genomic profiling-guided genome-matched therapy yielded encouraging results, with progression-free survival of 9.0 months in AYA versus 3.7 months in OA patients (P = 0.59). Our study suggests that tailored therapeutic approaches can benefit cancer patients regardless of age.