Using biomarkers to match therapies to advanced and/or refractory cancers is most likely to succeed when it is supported by strong clinical trial evidence, a new study from an Australian team showed.
They also found that only a minority of patients received genomically matched therapies, and even fewer received therapies backed by the highest level clinical evidence. Patients with advanced/refractory cancers who received therapies based on biomarkers had better overall survival only when there were supporting prospective studies for their use.
“There is a growing gap when it comes to figuring out how to accurately pair the right drug with the right patient. Simply having a genomic report and an available drug is not enough,” the study’s lead author Frank P. Lin, MBChB, PhD, told Inside Precision Medicine. Lin is Senior Research Officer, Garvan Institute of Medical Research. The team’s study appeared in JAMA Oncology last week.
He added that, “Often the most significant, translational obstacle to the clinic is the lack of a coherent decision-making strategy that pragmatically optimizes the value of these tests during patient encounters and Molecular Tumour Board (MTB) discussions. This is exactly what our paper studied. We have demonstrated the added value of a structured way of thinking through treatment options when facing complex molecular reports.”
Multiple studies have shown that therapies selected using biomarkers can improve cancer outcomes, but results have been inconsistent. These authors analyzed data using the screening tool of the Australian Molecular Screening and Therapeutics (MoST) study, a nationwide precision oncology program that uses genomic profiling of archival tissue to find useful biomarkers for advanced or rare cancers.
The study included data from adults enrolled in the MoST program from June 2016 to December 2021 and followed through July 2022. Investigators compared survival in patients who received therapies selected on the basis of TOPOGRAPH guidelines evidence levels 1-3A against those treated with therapies supported only by investigative studies or using repurposed drugs (evidence tiers 3B/4).
It included 3,383 patients, 3,003 of whom had at least one genomic biomarker for which a tier 1-4 therapy could be matched. That group included 1,270 (37.5%) with clinically active biomarkers (tiers 1-3A).
Median overall survival improved from 12.8 months to 21.2 months when evidence-based therapies were selected using TOPOGRAPH. However, when therapies were matched to cancers only on the basis of “investigational” evidence (such as studies in other tumor types or preclinical work) survival was not significantly improved. Further, patients who received therapies repurposed based solely on biomarker detection, without trial evidence, also did not live longer than those who did not get such treatments.
While the study shows the value of the precision medicine approach, it also reinforces the need for more and better biomarkers as well as cancer drugs, said Lin. “Oncologists always need better, highly predictive biomarkers paired with specific treatments, and the incremental value of this is highest in rare and refractory cancers.”
Vivek Subbiah, MD, of the Sarah Cannon Research Institute in Nashville, authored an accompanying editorial. He noted that the Australian study included patients treated from 2016-2021, a period when many targetable genomic variants had few if any available therapies.
