Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Breast Cancer

Treatment: FoundationOne CDx (broad companion diagnostic) molecular panel testing (genetic testing of tumor tissue to identify targeted cancer treatment)

The insurer denied coverage for FoundationOne CDx molecular panel testing (genetic testing of tumor tissue to identify targeted cancer treatment).

The denial is upheld.

The patient is a female with a history of metastatic breast cancer diagnosed. She was treated with chemotherapy and radiation. The provider ordered the FoundationOne testing to further guide the course of treatment. Molecular profiling for malignant tumors catalogues specific biomarker information and generates potential treatment options. The personalized tumor molecular profiling services or tests are similar in that they all take an individual's tumor tissue and, from it, produce a molecular profile of the tumor and a list of potential therapies.

For individuals who have cancers that have not responded to standard therapy who receive testing of tumor tissue with an expanded cancer mutation panel, the evidence includes 1 randomized controlled trial (RCT), nonrandomized trials, and numerous case series. The clinical validity of the individual mutations for particular types of cancer is not easily determined from the published literature. The large number of mutations and many types of cancer preclude determination of the clinical validity of the panels as a whole. Some evidence has reported that many of the identified mutations are false positives (i.e. ["that is"], not biologically active). 

To be clinically useful, direct evidence from interventional trials are needed that compare targeted treatment based on panel results with standard care. The first such published RCT reported that there was no difference in progression-free survival when panels were used in this way. Some nonrandomized comparative studies, comparing matched treatment with nonmatched treatment, have reported that outcomes are superior for patients receiving matched treatment. However, these studies are inadequate to determine treatment efficacy because the populations with matched and unmatched cancers may differ on several important clinical and prognostic variables. In addition, there is potential for harm if ineffective therapy is given based on test results, because there may be adverse effects of therapy in absence of a benefit. 

In summary, the evidence is insufficient to determine the effects of the technology on health outcomes. There is insufficient published data to determine the impact on health outcomes of targeted treatment based on expanded tumor marker panels compared to standard of care for cancer types other than non-small cell lung cancer and therefore the Foundation One test was not medically necessary, and it is still considered experimental/investigational.

The scientific evidence in peer-reviewed literature does not support a result of improvement in health outcome. FoundationOne CDx molecular panel testing (genetic testing of tumor tissue to identify targeted cancer treatment) has received approval from the FDA (Food and Drug Administration) (i.e., after the test was performed on this patient) to be used as a companion diagnostic to identify patients with Microsatellite Instability High (MSI-H) status solid tumors who may be appropriate for treatment with Merck's Keytruda (pembrolizumab). In other words, it is not approved for managing this patient. This patient is not a good candidate for FoundationOne CDx molecular panel testing (genetic testing of tumor tissue to identify targeted cancer treatment).

In summary, FoundationOne CDx molecular panel testing (genetic testing of tumor tissue to identify targeted cancer treatment) is not likely to be more beneficial than any standard treatments for this patient's condition and the adverse risks may be increased over standard treatments. 

The carrier's denial of FoundationOne CDx molecular panel testing (genetic testing of tumor tissue to identify targeted cancer treatment) should be upheld.