Tumor-agnostic molecular profiling extends survival in refractory cancers by 40% in phase 2 cohorts

The approach relies on large-scale NGS panels applied at diagnosis or progression. In the NCI-MATCH and TAPISTRY trials, patients with rare alterations (NTRK fusions, BRAF V600E, MSI-high) received matched agents irrespective of primary site. Objective response rates reached 30-50% in multi-histology cohorts where standard chemotherapy yields <10%. Real-world data from 4,000+ patients in the AACR GENIE registry confirm median overall survival gains of 8-14 months when actionable drivers are present and treated. These results overturn the organ-centric model that dominated oncology for decades. Key limitations include assay turnaround time averaging 18 days and under-representation of underrepresented ancestries in trial enrollment. Ongoing adaptive platform studies such as I-PREDICT and CUPISCO aim to close these gaps by mandating liquid biopsy reflex testing and ancestry-stratified randomization. Regulatory expansion of tumor-agnostic labels is expected once 12-month progression-free survival data mature in 2025.