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85 percent of patients with cancer of unknown origin matched to treatment using new gene test

, has announced that new data utilizing FoundationOne was published in the inaugural issue of . The peer-reviewed paper, titled “Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Site Reveals New Routes to Targeted Therapies,” presents data from a retrospective study of 200 diagnosed with cancer of unknown primary origin (CUP) in which FoundationOne identified clinically relevant genomic in 85 percent of patients. Importantly, each of those patients harbored at least one genomic alteration that could be matched to approved targeted therapies or to investigational anti-cancer therapies currently in clinical trials, providing physicians with an immediate opportunity to influence therapy decisions and potentially improve outcomes for individuals living with CUP.

Today, CUP represents an area of critically high medical need: there are no FDA-approved therapies, and one- and five-year relative survival rates are estimated at 23 and 10.6 percent1, respectively. Recent evidence suggests that determining the tissue of origin of an unknown primary cancer may be less relevant than delineating the driver of genomic alterations that are fueling disease progression2. Therefore, comprehensive genomic profiling with FoundationOne could potentially offer a new, immediate and vitally important approach to the treatment and care management of individuals with CUP.

“Searching for the primary site of origin in patients with CUP is often a costly, time-consuming and sometimes futile process,” said Jeffrey S. Ross, M.D., Medical Director of Foundation Medicine and Chair of Pathology at Albany Medical Center, and lead author of the paper. “Our findings reveal that by utilizing FoundationOne, a singular comprehensive approach, we were able to uncover an extremely high rate of clinically relevant genomic alterations, while eliminating numerous costly and time-consuming diagnostic analyses. By identifying potential targeted therapeutic options that may be more effective and less toxic than standard therapies, we can bring new hope to individuals with CUP.”

A summary of key findings from the manuscript include:

  • The paper highlights individual cases in which outcomes could be ascertained and where CUP patients were known to have experienced benefit from treatment by targeted therapies that were identified by FoundationOne, including:
  • MET amplification in a patient who presented with new onset seizures. Treatment with crizotinib led to an ongoing complete clinical response currently exceeding two years
  • A patient who achieved a major response to targeted therapy when comprehensive profiling was performed “up-front” and revealed an ALK fusion that responded dramatically to crizotinib
  • Of 200 patients with CUP, 96 percent (192/200) harbored at least one genomic alteration
  • A total of 841 alterations were identified in 121 genes for a mean of 4.2 alterations per patient
  • Importantly, 85 percent of all patients (169/200) were found to have at least one clinically relevant genomic alteration; many of these alterations could be associated with approved anti-cancer drugs such as erlotinib, crizotinib or vemurafenib or with an active clinical study
  • CUP is the clinical term used when is found, but the site where the cancer began cannot be determined. More than 30,000 patients in the United States each year, or between two and nine percent of all cancer patients, have a cancer whose primary site is never identified3. There are no drugs specifically approved for CUP, and patients are commonly treated with multi-agent cytotoxic chemotherapy4, a non-targeted approach associated with a modest response rate and a poor five-year survival5. The cost of a complete diagnostic workup for patients with CUP, including multimodality diagnostic imaging procedures, tissue IHC panels, serum tumor marker panels and mRNA profiling, commonly exceeds $10,000. For many of these patients, even after a thorough workup, determining the primary tumor site may be impossible or uninformative, and often treatment guided by knowing only the primary site does not improve outcomes or prognosis.

    Foundation Medicine is performing retrospective analyses and planning prospective studies to determine the health economic benefit and clinical outcomes, which result from performing comprehensive genomic profiling with FoundationOne for individuals with CUP.


    1. Surveillance, Epidemiology, and End Results (SEER) Program (http://www.seer.cancer.gov). SEER Stat Database: Incidence – SEER 9 Regs Research Data, Nov 2013 Sub (1973-2011).

    2. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley  TJ, Wilson RK, Raphael BJ, Ding L. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502:333-9.

    3. Greco FA, Hainsworth JD: Cancer of unknown primary. In Cancer: Principles and Practice of Oncology.

    4. Stella GM, Senetta R, Cassenti A, Ronco M, Cassoni P. Cancers of unknown primary origin: current perspectives and future therapeutic strategies. J Transl Med. 2012;10:12.

    5. Varadhachary GR, Raber MN. Cancer of unknown primary site. N Engl J Med. 2014;371:757-765.

    Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Site New Routes to Targeted Therapies, Jeffrey S. Ross, MD; Kai Wang, MD, PhD; Laurie Gay, PhD; Geoff A. Otto, PhD; Emily White, BS; Kiel Iwanik, BS; Gary Palmer, MD; Roman Yelensky, PhD; Doron M. Lipson, PhD; Juliann Chmielecki, PhD; Rachel L. Erlich, PhD; Andrew N. Rankin, PhD; Siraj M. Ali, MD, PhD; Julia A. Elvin, MD, PhD; Deborah Morosini, MD; Vincent A. Miller, MD; Philip J. Stephens, PhD, JAMA Oncology, doi:10.1001/jamaoncol.2014.216, published online 12 February 2015.

    Source: Foundation Medicine