NEW YORK – New research suggests cancer patient outcomes and precision treatment options can be enhanced by using pathologist-directed tumor profiling focused on actionable alterations across hundreds of genes linked to targeted treatment or immunotherapy response.
For a study published in the Journal of Clinical Oncology-Oncology Practice on Tuesday, researchers at the national non-profit Catholic health system Providence Health, along with colleagues at Illumina and Microsoft Research, considered outcomes for 3,216 stage III or stage IV cancer patients between the ages of 60 and 75 who received free tumor testing using "Gene ProvSeq" Comprehensive Genomic Profiling (CGP).
The laboratory-developed, pathologist-initiated, next-generation sequencing assay uses hybrid capture and the Illumina NovaSeq 6000 to assess both DNA and RNA sequences for 523 potentially targetable genes.
"This workflow replaced a previous methodology largely using oncologist-directed small panel testing (5-50 genes)," the authors explained. "By shifting next-generation sequencing (NGS) upstream, we could facilitate use of test results in the diagnostic process and make results available earlier to the treating physician."
Based on findings from the CGP, coupled with clinical decision support tools, the team identified patients with actionable genomic biomarkers. From there, the group relied on a natural language processing tool developed at Microsoft to investigate the clinical implications of the approach in the advanced cancer cohort.
Compared to an in silico set of just 50 tumor genes that would have picked up clinically actionable alterations in some 33 percent of the tumors tested, for example, the CGP panel picked up clinically actionable alterations in up to 67 percent of tumors tested.
In particular, the investigators found that CGP profiling uncovered biomarkers for approved treatments — including targeted treatment or immunotherapy — in 1,568 of the patients considered. More than one-fifth of the tumors were marked by a high tumor mutational burden, while targetable BRAF and EGFR alterations turned up in 11 percent and 4 percent of the tumors, respectively.
When they considered eligibility for ongoing basket clinical trials that match patients to treatment based on targeted tumor alterations, meanwhile, they found that 1,710 CGP-profiled patients had tumor mutations that matched them to at least one arm of the ASCO, NCI-MATCH, or MyPathway trials — up from the 843 patients who would have been found using an in silico 50-gene tumor profiling panel.
Similarly, the use of targeted treatment or immunotherapy was documented for more than half of patients followed for six months or longer, compared to chemotherapy alone for 32 percent of patients.
The team also saw increased overall survival (from 17 months to 25 months) in patients who received targeted treatment rather than conventional chemotherapy alone when it focused on outcomes in 1,482 stage IV, CGP-profiled patients with available follow-up and treatment information over eight to 21 months.
"By getting CGP test results in the hands of pathologists and oncologists at the onset of a cancer diagnosis, we witnessed CGP-tested patients received biomarker-matched therapy at a higher rate, which often led to better outcomes," co-author Carlo Bifulco, chief medical officer with Providence Genomics, said in a statement.
The authors noted that participants in the current study received the CGP testing at no charge within a research protocol to remove treatment challenges related to reimbursement.
"By removing the barrier that most often prevents patients from receiving this test, we were able to observe a sizeable cohort and witness the effectiveness of tumor molecular profiling and the precision therapies that often followed," first author Alexa Dowdell, a bioinformatics researcher with Providence, said in a statement.