By Stephanie Murg, Managing Director of Conferences, G2 Intelligence
Last Thursday marked the debut of JAMA Oncology, which will be published online each week before premiering as a monthly formal print/online issue beginning in April, and among the first published studies investigated the applications of genomic profiling to cancer of an unknown primary site (CUP). The study found at least one clinically relevant genomic alteration in most of the samples tested, an indication of potential to guide and personalize therapy for this type of cancer, which responds poorly to nontargeted chemotherapy treatments.
Previous studies of CUP, which is diagnosed in more than 30,000 patients each year in the United States alone, have relied primarily on immunohistochemical analysis and gene expression (mRNA) profiling. In this study, Jeffrey S. Ross, M.D., of Foundation Medicine (Cambridge, Mass.) and Albany Medical College (Albany, N.Y.), and coauthors used the hybrid-capture-based FoundationOne assay to perform genomic profiling on 200 CUP samples to look for targetable genomic alterations that might identify opportunities to target therapies for patients with CUP.
The researchers identified at least one genomic alteration in 96 percent of the CUP specimens. Within the 200 samples, a total of 841 alterations were identified in 121 genes. Additionally, one or more potentially targetable genomic alteration was identified in 85 percent of CUP specimens. Future studies will likely aim to confirm these observations in prospective randomized clinical trials.
In light of the poor prognosis of CUP treated by nontargeted conventional therapies, the authors conclude that “comprehensive genomic profiling shows promise to identify targeted therapeutic approaches to improve outcomes for this disease while potentially reducing the often costly and time-consuming search for the tumor’s anatomic site of origin.”
“From a development perspective, it is especially encouraging that several molecular targets may be independent of the tumor site, making it possible to include patients with CUP in new studies of targeted therapies and allowing us to piggyback on the broader advances in personalized cancer therapy,” notes Gauri Varadhachary, M.D., of the University of Texas MD Anderson Cancer Center (Houston) in an accompanying editorial in JAMA Oncology. “Just as we need to be selective in our diagnostic approach using an effective algorithm that leverages the proteomics and genomics techniques, we need to be selective in our research efforts to deliver validated new approaches to our patients with CUP.”