Original Investigation

Genomic Therapy Matching in Rare and Refractory Cancers

JAMA Oncology 10.1001/jamaoncol.2026.0127

March 05, 2026 at 11:00 AM EST

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In patients with advanced, refractory cancers, is a tiered framework for matching genomic biomarkers to therapies associated with improved survival?In this cohort study of 3383 patients with advanced solid tumors, those with biomarkers supported by prospective trial evidence who received matched therapy had a median overall survival of 21.2 months vs 12.8 months for those receiving unmatched therapy. No survival benefit was observed for therapies matched using preclinical evidence or repurposed from other cancer types.These findings support prioritizing genomically guided therapies based on the strength of clinical evidence, as only matches supported by prospective trials were associated with a survival benefit.

Corresponding Authors: Frank P. Lin, MB ChB, PhD, NHMRC Clinical Trials Centre, University of Sydney, Lifehouse Building, Level 6, 119-143 Missenden Rd, Camperdown, NSW 2050, Australia (frank.lin@sydney.edu.au); David M. Thomas, MBBS, PhD, Centre for Molecular Oncology, UNSW Sydney, Wallace Wurth Building, Level 5, Kensington Campus, UNSW Sydney, Kensington, NSW 2052, Australia (dmthomas@unsw.edu.au).

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