A prospective study has used whole genome and transcriptome analysis (WGTA) for real-time treatment options in cancer patients. Published in Annals of Oncology, the study used samples from over 500 patients with advanced or metastatic cancer. WGTA insights informed the selection of therapeutics and demonstrated a clinical benefit to patients.
“We show how RNA and DNA information alone and in combination contribute to treatment with tailored therapy across all tumour types,” write the authors.
Canadian-based prospective trial
Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program. POG is a single arm prospective trial approved by the University of British Columbia Cancer Research Ethics Board. POG samples underwent whole genome and transcriptome analysis.
DNA-based and RNA-based data were combined to create comprehensive WGTA profiles. The profiles were then used to identify and prioritise clinically actionable alterations and inform therapy.
A multidisciplinary molecular tumour board (MTB) discussed the possible actionable therapeutic options. This incorporated clinical and pathology data for each patient. WGTA-informed therapies were accessed through clinical trials, off-label, or as prioritised standard of care options. Patients were then assessed for clinical benefit.
RNA data as valuable as DNA data
Genomic information was considered clinically actionable if a target or risk factor that potentially affected the treatment plan was identified. Clinically actionable targets were identified for 83% of patients. 37% of these received whole genome and transcriptome analysis informed treatments.
Patients accessed WGTA-informed treatments through clinical trials, off-label use, and as standard therapies. This included those which would not otherwise have been the next choice of therapy.
Out of 248 WGTA-informed treatments, 46% resulted in clinical benefit to the patient. This result was seen despite the advanced nature of disease and prior treatment history of many patients.
The researchers found that RNA expression information was as valuable as DNA-based information for selecting treatments with clinical benefit.25% of treatments were informed by RNA expression alone.
For 5% of patients, WGTA revealed a previously known actionable alteration without providing additional insight. In these instances treatment was not counted as WGTA-informed. Of those that did not receive WGTA-informed therapy, the most common reasons were that the treatment was not accessible including due to location or cost, or due to the patient being too ill to receive the treatment.
WGTA informed therapeutic options
Although it was not a focus of this study, the authors raise that there is the potential for using WGTA information to avoid ineffective treatment when there is evidence for resistance.
The authors conclude, “In the majority of cases in which WGTA-informed treatments were accessible as standard of care in our cohort, clinicians used WGTA to change their decision about the next standard treatment. This demonstrates that the use of WGTA data is not limited to expensive targeted therapies but can be used to identify accessible, cost effective standard treatments.”
Written by Poppy Jayne Morgan, Front Line Genomics
Image Credit: Canva