Genomically Matched Cancer Therapies Only as Good as Supporting Evidence

Survival in advanced/refractory cancers improved significantly when patients received genomically matched therapies supported by clinical trial evidence.

Published on Mar. 5, 2026

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A large multicenter cohort study from Australia found that patients with advanced or refractory cancers treated with genomically matched therapies had better overall survival only when the treatments had support from prospective studies. Genomically matched therapies associated with investigational evidence only did not improve survival versus unmatched therapies.

Why it matters

The results support an evidence-based approach to prioritize genomically guided therapies for cancer, as the ability to detect and study genetic aberrations in tumors has led to the development of many new cancer therapies. However, a lack of standardized definition of "actionability" of genomic alterations has resulted in inconsistent outcomes.

The details

The study analyzed data from the Australian Molecular Screening and Therapeutics (MoST) program, a nationwide precision oncology program that uses genomic profiling to identify actionable biomarkers for patients with advanced or rare cancers. Patients were stratified into two cohorts: those who received no further systemic therapies and those who received systemic therapy after genomic profiling. Overall, patients who received a matched therapy had a significantly longer overall survival (OS) compared to those who received unmatched therapies. However, patients who received only therapies supported by investigational studies did not have a significant reduction in the survival hazard compared to the unmatched group.

  • The analysis included adults enrolled in the MoST program from June 2016 to December 2021 and followed through July 2022.
  • The study population had a median follow-up of 22.6 months.

The players

Frank P. Lin

MBChB, PhD, of the University of Sydney, and lead author of the study.

Vivek Subbiah

MD, of the Sarah Cannon Research Institute in Nashville, Tennessee, and author of the accompanying editorial.

Australian Molecular Screening and Therapeutics (MoST) program

A nationwide precision oncology program that uses genomic profiling to identify actionable biomarkers for patients with advanced or rare cancers.

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What they’re saying

“We observed a 40% reduction in the risk of death associated with the receipt of genomic-matched therapy in the clinically active tier group [TOPOGRAPH tiers 1-3A] after accounting for confounders and time-related biases.”

— Frank P. Lin, MBChB, PhD, of the University of Sydney (JAMA Oncology)

“By transforming the binary question of [biomarker] actionability into a nuanced inquiry about evidence strength, the investigators provide oncologists with a sophisticated decision-making tool beyond simple lists of druggable variants.”

— Vivek Subbiah, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee (JAMA Oncology)

What’s next

The study authors note that the lack of benefit for tier 3B and 4 matches might have reflected the limited availability of drugs during the study period, and that the observed benefits may have been attenuated by the fact that the study included patients treated from 2016-2021, when many targetable genomic variants had few if any available therapies.

The takeaway

This study highlights the importance of an evidence-based approach to precision oncology, where the strength of supporting evidence for genomically matched therapies is a key factor in determining their clinical benefit. It suggests that simply identifying genomic alterations is not enough - oncologists need to prioritize therapies backed by robust clinical trial data to maximize the chances of improving survival for patients with advanced or refractory cancers.