By Clinical Informatics News Staff 

January 9, 2014 | Foundation Medicine of Cambridge, Mass., continues to make the case for expansive next-generation sequencing (NGS) tests as the front line of cancer diagnostics, with a new publication in Clinical Cancer Research co-authored by members of the company and researchers at Memorial Sloan Kettering Cancer Center (MSKCC). The paper attempts to quantify the incremental benefit of choosing these NGS assays when designing a cancer treatment regimen, by retesting patients who had previously tested negative for actionable tumor mutations in a wide array of traditional, cancer type-specific assays.

MSKCC recruited 31 patients for the study, all non-smokers or light smokers with lung adenocarcinomas in late stages of disease progression or with clinical signs that pointed to a high risk of recurrence. Each had gone through a large battery of co-diagnostic tests for targeted lung cancer therapies—including a Sequenom multiplex mass spec assay, multiplex sizing assays, and FISH probes, together covering 11 different genes—without discovering an actionable mutation. Tissue samples from each patient were then sent to Foundation Medicine to undergo a FoundationOne solid tumor NGS test.

The headline result of the study was that, for a majority of enrolled patients, clinicians received some actionable treatment guidance as a result of the FoundationOne test: either an FDA-approved targeted therapy as recommended by the National Comprehensive Cancer Network (8 patients), or an experimental treatment from an MSKCC clinical trial or off-label drug application (12 patients). Seven patients ultimately received a new targeted therapy after testing, and MSKCC considers a further 12 as candidates for a targeted therapy upon progression. This finding could be considered highly relevant, suggesting that most non-smoking lung adenocarcinoma patients failed by the standard of care in co-diagnostic testing could be given new treatment options if offered a broad NGS panel. NGS testing could also catch any mutations currently diagnosed using other methods, while using smaller tissue samples potentially gathered through less invasive procedures. Indeed, MSKCC has gone on to make FoundationOne and similar tests its front line standard for a variety of cancers.

Adenocarcinomas in non-smokers may not be representative of cancers as a whole. For one thing, this is a cancer type with an unusually rich set of targeted therapies already widely accepted by oncologists. For another, lung tumors in non-smokers tend to have fewer mutations in a narrower range of genetic pathways than those in smokers, making it more likely that any given mutation found with an NGS panel will be actionable. However, studies like this emphasize that the medical community may not be taking full advantage of targeted therapies already available, even in patient populations that have benefited most from the rapid expansion in co-diagnostic tests and gene-based drug discovery.

Foundation Medicine, one of the most prominent providers of NGS testing in cancer, has recently focused heavily on validating the clinical utility and cost effectiveness of its approach to cancer diagnostics. Still in the works is a partnership with Cancer Outcomes Tracking and Analysis, also centered on late-stage adenocarcinoma, which plans to track not only the diagnosis rate of the FoundationOne test, but also long-term patient outcomes and cost data.