Targeted Therapy, Immunotherapy, and Molecular Testing in Advanced Solid Tumors: A Medicare Analysis.

BACKGROUND AND PURPOSE: Biomarker testing and matched therapies are central to precision oncology, but their real-world uptake and clinical impact among older adults with advanced solid tumors remain poorly characterized. This retrospective observational cohort study assessed biomarker testing and guideline-concordant matched first-line therapy use and evaluated their associations with overall survival, diagnosis-to-treatment intervals, and 6-month physical functioning in these patients. MATERIAL AND METHODS: This study used linked US Medicare claims, electronic medical records, and patient-reported outcomes of fee-for-service beneficiaries ≥ 65 years with incident advanced/metastatic non-small cell lung cancer, breast, colorectal/gastric, or urothelial cancer. Biomarker testing (≤ 30 days pre-diagnosis through first-line therapy initiation) and guideline-concordant matched targeted or immunotherapy-based first-line treatment (defined as first-line initiation of a targeted or immuno-oncology agent whose approved indication corresponded to the patient's actionable biomarker within the study period [Table S5]) were assessed. Primary outcomes were overall survival, time to first-line therapy, and 6-month physical functioning. Associations were estimated using inverse probability-weighted Cox proportional hazards and marginal structural models; residual confounding was probed with E-values and landmark sensitivity analyses. RESULTS: Among 39,964 beneficiaries with advanced cancers, 21.6% underwent biomarker testing. Actionable alterations were identified in 9.8% of patients, of whom 62.0% received matched first-line therapy. Testing modestly increased median diagnosis-to-treatment intervals, but delays beyond tumor-specific medians were not associated with excess mortality. Biomarker testing was associated with longer overall survival, and matched first-line therapy was associated with higher 6-month physical functioning across all cohorts (p < 0.001). INTERPRETATION: Biomarker testing and matched first-line therapies were underused but associated with longer overall survival and better physical functioning. Residual confounding is possible and the magnitude of the testing-survival association likely partially reflects selection of fitter patients into testing. Modest testing-related treatment delays were not associated with worse survival, supporting expansion of routine biomarker testing in Medicare oncology practice.