Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Esophageal Cancer.
Treatment: FoundationOne CDx (broad companion diagnostic) panel genetic testing.
The insurer denied coverage for FoundationOne CDx panel genetic testing.
The denial is upheld.

This patient is a male with esophageal cancer involving the regional lymph nodes, a clinical-stage known to be programmed death ligand 1 (PD-L1) positive based on testing done on the original path specimen, with prior therapy of folinic acid, fluorouracil, and oxaliplatin (FOLFOX). The treating provider performed Foundation One testing "even though the chance of targetable mutations is low in squamous cell cancer". 

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. 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 2 (HER2)] and then claiming that the identification and targeting of said known drivers contribute 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 an experimental therapy for the reasons outlined above. Standard testing for esophageal cancer would include PD-L1 which was already performed.

"Although these results are preliminary, significant discordance also has been noted between reports comparing tissue-based next-generation sequencing tests and, in a recent report, between results from FoundationOne (F1) and Guardant360 (G360) testing. Our findings indicate that in-depth comparisons of next-generation sequencing tests across larger numbers of patients with cancer are needed to improve concordance and clinical utility." (Kuderer, N. M. et al. 2017)

Although Frampton, G.M., et al. (2013), 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 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."

The Foundation One CDx panel genetic testing is not considered medically necessary for this patient. National Comprehensive Cancer Network (NCCN) notes that selective testing is appropriate. They note the need for comprehensive genomic profiling via NGS if there is limited pathologic tissue or the patient is unable to undergo biopsy which was not the case for this patient.  

The health plan acted reasonably with sound medical judgment in the best interest of the patient.

The insurer's denial of coverage for FoundationOne CDx panel genetic testing is upheld. Medical Necessity is not substantiated.