Matching cancer therapies to tumour genomic alterations was associated with longer survival in patients with advanced cancers when the biomarker–drug pairing was supported by prospective clinical evidence, according to results from a large Australian precision oncology program published in JAMA Oncology.
The cohort study analysed outcomes from the Molecular Screening and Therapeutics (MoST) program, a nationwide Australian precision oncology initiative designed to identify actionable genomic alterations and match patients with targeted therapies or clinical trials.
CLINICAL SUMMARY
What was examined
A cohort study of 3383 patients with advanced solid tumours enrolled in the Australian Molecular Screening and Therapeutics (MoST) precision oncology program assessed whether matching therapies to genomic biomarkers was associated with improved survival according to the level of supporting clinical evidence.
Key findings
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Patients receiving genomically matched therapy supported by prospective clinical trial evidence had longer median overall survival than those receiving unmatched therapy (21.2 vs 12.8 months).
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No survival advantage was observed when therapies were matched using investigational evidence or cross-tumour extrapolation.
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Approximately 37.5% of patients had genomic biomarkers supported by higher-level clinical evidence.
Clinical implications
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Precision oncology strategies may be most informative when biomarker–drug pairs are supported by robust clinical evidence.
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Matching therapies based primarily on biological plausibility or limited evidence may not translate into improved outcomes.
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Evidence-based frameworks may help guide treatment prioritisation within molecular tumour boards and precision oncology programs.
Researchers evaluated 3383 patients with advanced solid tumours, most of whom had refractory disease, who underwent comprehensive genomic profiling through the program. The analysis included patients enrolled between July 2016 and December 2021.
In routine practice, molecular tumour boards frequently face decisions about whether genomic alterations identified through sequencing should guide therapy selection. However, the strength of clinical evidence supporting specific biomarker–drug matches varies widely, particularly when therapies are extrapolated across tumour types.
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To assess the clinical impact of genomic matching, investigators used the TOPOGRAPH knowledge base, an Australian framework that ranks biomarker–drug associations according to the level of supporting clinical evidence.
Among the study population, 1270 patients (37.5%) had biomarkers supported by prospective clinical trial evidence (tiers 1–3A) indicating potential sensitivity to targeted therapy.
Patients with higher-evidence biomarkers who received genomically matched therapy had longer median overall survival than those receiving unmatched therapy
Patients with higher-evidence biomarkers who received genomically matched therapy had longer median overall survival than those receiving unmatched therapy (21.2 months versus 12.8 months; adjusted hazard ratio 0.60; 95% CI 0.44–0.82).
In contrast, when treatment decisions were based on lower levels of evidence, including investigational biomarker–drug matches or therapies extrapolated from other tumour types, no survival benefit was observed. Patients receiving these lower-evidence matched therapies had outcomes similar to those receiving unmatched treatment.
For example, therapies matched using investigational evidence alone (tiers 3B or 4) were not associated with improved survival compared with unmatched therapy (median overall survival 14.5 months versus 12.8 months).
Only a minority of patients ultimately received genomically matched therapy, reflecting ongoing challenges in access to targeted treatments and clinical trials within precision oncology programs.
The findings highlight an important distinction in precision oncology: while genomic profiling frequently identifies potentially actionable alterations, the clinical value of matching therapies may depend heavily on the strength of supporting evidence for the biomarker–drug pairing.
The authors note that precision oncology programs often rely on varying levels of evidence when recommending targeted therapies, particularly for patients with rare cancers or heavily pre-treated disease where standard treatment options are limited.
According to the investigators, the results suggest that genomic treatment strategies supported by prospective clinical trial data may warrant prioritisation within precision oncology programs, compared with approaches based primarily on biological rationale or cross-tumour extrapolation.
As an observational analysis within a precision oncology program, the study cannot establish causality. Differences in patient characteristics, access to therapies, and participation in clinical trials may also have influenced outcomes.
Taken together, the findings contribute to ongoing efforts to define how genomic profiling should be integrated into routine oncology care. The authors suggest that evidence-tier frameworks such as TOPOGRAPH may help guide molecular tumour boards in prioritising treatment options as precision oncology programs continue to expand.
Paper: Lin FP, Thavaneswaran S, Grady JP, et al. Genomic Therapy Matching in Rare and Refractory Cancers. JAMA Oncol. Published online March 05, 2026. doi:10.1001/jamaoncol.2026.0127 Access online here.
