Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Breast Cancer
Treatment: Genetic Testing (Foundation One CDX) 
The insurer denied the Genetic Testing (Foundation One CDX). 
The denial is upheld.

The patient is a female with metaplastic breast cancer. Her provider has requested coverage for Foundation One testing.

No, the health plan should not cover the requested genetic testing.

No, the genetic testing is not likely to be more beneficial.

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. [that is], breast cancer with ER [estrogen receptor] and HER2 [human epidermal growth factor receptor 2]), 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 experimental 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% (percent) 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 breast 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."

Per 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."

Per Singh, et al, "Overall, our study provides a real-world experience of the impact of CGP [comprehensive genomic profiling] in a community-based academic NCI [National Cancer Institute]-designated 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. 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. [for example], recent studies do suggest expanding impact in breast (PI3kinase inhibitors) and pancreatic malignancies (poly ADP ribose polymerase [PARP] inhibition). 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."

Therefore, given the above, this testing is likely to lead at attempts to the use of off-label therapy of no established clinical benefit.