Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Breast Cancer
Treatment: FoundationOne CDx genetic testing
The health plan denied: FoundationOne CDx genetic testing
The determination is: Upheld

The patient is a female with recurrent, metastatic, triple negative breast cancer. The patient has previously undergone a lumpectomy and adjuvant doxorubicin+cyclophosphamide therapy, followed by radiotherapy following her diagnosis. The patient developed a malignant pleural effusion. The recurrent cancer was found to be programmed death-ligand 1 (PD-L1) negative. The FoundationOne CDx assay was obtained at diagnosis and was unremarkable. This is being repeated; it is under review. In the interim, the patient is receiving single agent Abraxane.
At issue is the medical necessity of FoundationOne CDx genetic testing.
The health plan's determination of medical necessity is upheld in whole.
The requested health service/treatment of FoundationOne CDx genetic testing is not medically necessary for this patient.
The use of next generation sequencing (NGS) gene panels to guide the treatment of patients with early line metastatic breast cancer has not been demonstrated to be of benefit. The assay in question is Food and Drug Administration (FDA) approved. Several ongoing trials (the National Cancer Institute [NCI] Molecular Analysis for Therapy Choice [MATCH] and the American Society of Clinical Oncology [ASCO] Targeted Agent and Profiling Utilization Registry [TAPUR] trials) are using next-generation sequencing of multiple genes (gene panel tests) to identify molecular abnormalities in the tumors of patients with refractory cancers that may potentially match molecularly targeted therapies that are either in clinical trials or approved for treatment of other cancer types.
To date, there is only one large, randomized trial to off-label use of molecularly targeted agents on the basis of identified molecular alterations for which results have been published in the peer-reviewed literature. The molecular profile of each patient's tumor was established with a mandatory biopsy of a metastatic tumor and large-scale genomic testing. Patients with an actionable mutation were randomized to receive a matched molecularly targeted agent (experimental group) or treatment at physician's choice (control group) by central block randomization (blocks of size six). Treatments in both groups were given in accordance with the approved product information and standard practice protocols at each institution and were continued until evidence of disease progression. The primary endpoint was progression-free survival in the intention-to-treat population. Median follow-up was 11.3 months in the experimental group and 11.3 months in the control group at the time of the primary analysis of progression-free survival. Median progression-free survival was 2.3 months in the experimental group versus 2.0 months. The conclusion of the authors was "...he 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 enrollment in clinical trials should be encouraged to assess predictive biomarkers of efficacy....
Another important point is that simply having a potentially targetable mutation does not guarantee that the patient will benefit from a therapy that presumably targets that mutation. Another potential pratfall is if targeted testing identifies a potentially actionable genetic abnormality for which a molecularly targeted treatment is available but not yet approved.
Based on the paucity of supporting data, neither the National Comprehensive Cancer Network (NCCN) nor the authors of UpToDate recommend the use of the FoundationOne CDx NGS assay in this clinical scenario (either once or twice). Treatment based on published literature and guideline recommendations has been encouraged.