Targeted Therapy, Immunotherapy, and Molecular Testing in Advanced Solid Tumors: A Medicare Analysis
Onur Baser, Yijia SunABSTRACT
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 ]) 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.