Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Cholagnigocarincoma.
Treatment: FoundationOne CDx Genetic Testing.
The insurer denied the FoundationOne CDx Genetic Testing.
The denial is upheld.

The patient is a female with cholangiocarcinoma. The attending physician
performed foundation one testing.

No, the proposed genetic testing was not medically necessary.
The use of next-generation sequencing (NGS) panel testing as a means to select
anti-cancer therapy in advanced cancer remains an area of active research with
ongoing studies of TPUR and MATCH. The concept of this approach is that all
cancers are unique and each cancer has a specific individual molecular driver
which can be identified using this testing. Once identified specific therapy can be
given to the patient directly treating their tumor. The majority of studies of this
approach are fraught with methodological design issues such as lack of
randomization and inclusion of large numbers of patients with established molecular
drivers (i.e. breast cancer with estrogen receptor [ER] and human epidermal growth
factor receptor two [HER2]) and then claiming that the identification and targeting of
said known drivers contributes to benefit. There has been only one well designed
trial of this approach, SHIVA which demonstrated that this testing approach does
not improve clinical outcomes for patients with advanced cancer. Therefore, this
would be considered unproven therapy for the reasons outlined above.

"Although Frampton, G.M., et al., noted with the use of this assay across the broad
spectrum of cancer cell line types resulted in "clinically actionable alterations" in
76% of tumors, at the moment there are no prospective or controlled trials showing
that the use of this information to direct therapy improves health outcomes for
patients with the diagnosis of renal cell cancer. In fact, the SHIVA study showed
that the use of broad molecular mutation testing to direct therapy resulted in no
improvement in progression free survival and the conclusion was that "off label use
of molecularly targeted agent should be discouraged."

Le Tourneau, C., et al., "The use of molecularly targeted agents outside their
indications does not improve progression-free survival compared with treatment at
physician's choice in heavily pretreated patients with cancer. Off-label use of
molecularly targeted agents should be discouraged, but enrolment in clinical trials
should be encouraged to assess predictive biomarkers of efficacy."

"Overall, our study provides a real-world experience of the impact of CGP
(comprehensive genomic profiling) in a community-based academic NCIdesignated (National Cancer Institute) cancer center serving a highly diverse
patient population, where molecular testing is based on a two-tier testing algorithm.
While recognizing that a 10% overall rate of management change that is based on
CGP (comprehensive genomic profiling) is very modest, its use in certain subsets,
such as advanced NSCLC (non-small cell lung cancer), where the impact currently
is most significant appears to be justifiable and it has been found to be cost
effective [40,41,42]. In addition, we have identified multiple reasons for the relatively
smaller clinical impact of CGP (comprehensive genomic profiling) in other tumor
types, despite a much larger proportion of patients with actionable genomic
alterations reported. The impact however is anticipated to be increasing in light of
new advances, e.g., recent studies do suggest expanding impact in breast
(PI3kinase inhibitors) and pancreatic malignancies (poly ADP ribose polymerase
(PARP) inhibition) [43,44,45,46,47]. Although issues, such as optimal timing,
access to clinical trials, and consolidating genomic testing need to be addressed at
an institutional level, reports from testing platforms need to be carefully interpreted
and ideally discussed in molecular tumor boards to provide the best treatment
option possible. More prospective trials are needed that would better inform our
choices for personalized treatment by providing assessments of overall survival and
quality of life with choosing targeted therapies that are based on CGP
(comprehensive genomic profiling) when compared to conventional therapies [11]."
(Singh, A.P., et al.).