Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Colon Cancer.
Treatment: Foundation One CDx genetic testing (0037Ux1).

The insurer denied the Foundation One CDx genetic testing (0037Ux1).
The denial is upheld. 

The patient is a male with metastatic colon cancer. A FoundationOne CDx test was performed on the tumor.

No, the proposed testing is not medically necessary.
The patient has metastatic colon cancer. A FoundationOne CDx test was performed on the tumor.

There are no clinical studies of the use of the FoundationOne CDx assay to direct therapy of colon cancer that demonstrate improved outcomes (www.pubmed.gov). 

Studies of tumor mutation panel testing of colorectal cancer only show that this testing is feasible but do not demonstrate that this testing improves patient management (Salem ME, Puccini A, Grothey A, Raghavan D, Goldberg RM, Xiu J, Korn WM, Weinberg BA, Hwang JJ, Shields AF, Marshall JL, Philip PA, Lenz HJ).

The National Comprehensive Cancer Network (NCCN) Guidelines for treatment of colon cancer do not include a recommendation for tumor mutation panel testing over individual mutation testing for Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and B-type Raf proto-oncogene (BRAF) V600E mutations (NCCN Guidelines, Colon Cancer). 

The standard of care in the United States does not yet include selecting chemotherapy for cancer based on the somatic mutation profile of the tumor. 

The use of tumor mutation panel test results to select targeted therapies for cancer was studied in a randomized clinical trial that compared the outcomes of treating patients with targeted agents based on panel test results versus conventional treatments (Le Tourneau C, Delord JP, Goncalves A, Gavoille C, Dubot C, Isambert N, Campone M, Tredan O, Massiani MA, Mauborgne C, Armanet S, Servant N, Bieche I, Bernard V, Gentien D, Jezequel P, Attignon V, Boyault S, Vincent-Salomon A, Servois V, Sablin MP, Kamal M, Paoletti X). The conclusions of this phase III study was that, "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."

Jones et al. analyzed the requirement for sequencing normal tissue in interpreting mutation panel sequencing of tumors. This study suggested that as many of 31% of "actionable" mutations in panels such as the FoundatioOne test might be "false positive". 

The use of next-generation sequencing panels for treatment selection for solid tumors was reviewed (Marrone M, Filipski KK, Gillanders EM, Schully SD, Freedman AN). This review concludes: 
"Currently, there is little information available on the post-analytic processes unique to next-generation sequencing platforms used by the companies offering these tests. Additionally, evidence of clinical validity showing an association between the genetic markers curated in these tests with treatment response to approved molecularly targeted therapies is lacking across all solid-tumor types. To date, there is no published data of improved outcomes when using the commercially available tests to guide treatment decisions."

The issue with the use of somatic panel mutation testing for selection of therapy for cancer is that the presence of mutation in a cancer of a given type does not imply a response to treatment with an agent that is targeting that mutation. 

As the efficacy of this testing is unproven, it would not be considered medically necessary.

The extensive panel mutation testing is of unproven benefit in the management of metastatic colon cancer. It is not medically necessary. It is not in the best interest of the patient to have tests performed that have not been shown to be helpful in directing the treatment of his cancer.