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Popular Cancer Gene Panels Give Widely Discordant Results

Hospital laboratories have been inundated with requests to send out specimens for next generation sequencing to identify cancer-associated mutations in the hope that an effective targeted therapy is available. These popular tests cost thousands of dollars but their clinical value has not been systematically studied. 

Recently, investigators from the University of Washington in Seattle sent specimens from 9 patients with advanced cancer to two different laboratories for analysis. Five patients had breast cancer and four other patients had pancreatic, lung, salivary gland, and thymic cancer. The two laboratories were Foundation Medicine and Guardant Health. FoundationOne sequences the exons of 315 cancer-associated genes and introns from 28 genes using tumor tissue. Guardant360 sequences 70 genes using cell-free circulating DNA. The investigators limited comparisons to alterations identifiable by both FoundationOne and Guardant360 testing.

The genomic alterations reported by both laboratories were compared for each patient. The results were also assessed to compare the recommended drugs. Unfortunately, this study revealed widely discordant results in the same patient. One patient had no genetic alteration identified by using either platform. The other 8 patients had 45 alterations, but only 10 (22%) were concordant between the platforms. Furthermore, for 2 of these 8 patients, there was zero concordance among the described alterations.

For the 8 patients, a total of 36 drugs were recommended. However, only 9 drugs (25%) were recommended for the same patients by both platforms. In 5 patients, there was no overlap between the drugs recommended by the FoundationOne test and those recommended by the Guardant360 test. In the majority of the patients, there was zero concordance in terms of drug recommendations.

Despite having a small sample size, this study was clinically relevant since both tests are performed in thousands of patients with cancer each year.  This study casts significant doubt on the benefit of genetic analysis of tumors for precision oncology.

Many critics have called for clinical trials to determine whether the rapidly expanding industry of cancer genetics testing actually improves patient outcomes. Treatments based on the results of these tests are almost never curative. They certainly do drive up health care costs.

Kuderer, NM et al. Comparison of 2 commercially available next-generation sequencing platforms in oncology. JAMA Oncol. Published online December 15, 2016. doi:10.1001/jamaoncol.2016.4983  Abstract

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