In community oncology practices, where most cancer in the United States is treated, broad-based genetic testing does not offer survival advantages compared with routine genetic testing for patients with advanced non-small cell lung cancer (NSCLC), concludes a new retrospective study.
But lung cancer experts challenge this conclusion, pointing out that few of the patients who were found to have actionable mutations on broad-based genetic testing actually received targeted therapy and some received targeted therapy not matched to the mutations.
The study, conducted by researchers at the Yale Cancer Center, New Haven, Connecticut, was published in JAMA Oncology. Using an "instrumental variable analysis," the retrospective analyses from a Flatiron Health Database showed that 12-month mortality was 41.1% for patients who received broad-based sequencing and 44.4% for those who received routine testing, and the difference between the two groups was not statistically significant.
The Flatiron Database provided data for 5688 patients with advanced NSCLC from 191 community oncology practices. Routine testing included testing for EGFR and/or ALK mutations, and broad-based testing included any multigene panel that tested more than 30 genes.
The results mean that "use of broad-based genomic sequencing in the community setting for advanced non-small cell lung cancer may not currently offer a survival advantage," the researchers conclude, implying that broad-based genetic testing in the community setting may not be warranted.
This conclusion may come as a shocker to those who treat NSCLC because in the current landscape of patient management, broad-based genetic testing has evolved as a tool to provide precision treatment and is recommended to match an actionable mutation with appropriate therapy.
Broad-based genetic testing
Indeed, guidelines for broad-based genetic testing are based on a plethora of studies that show an improvement in survival and/or clinical outcomes for patients who receive treatment that matches with a driver or actionable mutation in their tumor.
Bunn suggested that there is a gap in community oncology practices between getting mutational data and acting appropriately on it — a gap that may be associated with lack of clinician education or the unavailability of the appropriate therapy during the timeframe of the study. This gap results "in a potential study bias against broad-based genomic sequencing," Bunn and Aisner comment.
Shaw agreed that not all patients were matched to the appropriate targeted therapy. For example, she pointed out that patients with tumors that harbored MET or KRAS mutations were given erlotinib and patients who had CCNE1 orTAF1 mutations were given crizotinib (Xalkori, Pfizer). "Overall, the proportion of patients who received targeted treatment is small enough (4.5%) that even a few cases like these could skew the results," she said.
The researchers admit that decision support for oncologists in the community setting is needed and add that even if there is a potential clinical trial with an appropriate targeted therapy available, patient enrollment from a community setting is low.
"Efforts to increase access to broad-based genomic sequencing should be paired with efforts to facilitate clinical trial enrollment," the Yale researchers write. They also note that in the community setting the prohibitive cost of targeted therapies may result in financial burden and limit drug access.