Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Lung Cancer.
Treatment: Guardant360 Test.
The insurer denied the Guardant360 Test.
The denial is upheld.

The patient is a male who was diagnosed with metastatic non-small cell lung cancer (squamous cell carcinoma).  A Guardant360 liquid biopsy tumor mutation panel test was performed on the blood. This test was sent.  No further clinical information was provided. 

Two Medical Directors reviewed the request and determined there is not enough evidence in the medical literature to show that this testing improves clinical outcomes for patients with his condition. The health plan does not cover tests and treatments that are not shown to be medically necessary for his care. Coverage was denied as not medically necessary.

A letter of appeal was submitted by Guardant Health. This form letter of appeal did not explain how the testing performed benefited the patient. It contained no references that demonstrate that the use of Guardant360 testing will improve health outcomes. It did not explain why a liquid biopsy and not a solid tumor somatic mutation test was performed.

No, the proposed testing was not medically necessary.
The patient had metastatic non-small cell lung cancer (squamous cell carcinoma). There was no documentation of inadequate tumor tissue to perform solid tumor mutation panel testing. 

A Guardant360 test was performed on the patient's blood at the time of diagnosis.  The codes in question were billed for the Guardant360 test. 

The National Comprehensive Cancer Network (NCCN; URL: www.nccn.org) is an organization whose members are drawn from the nation's National Cancer Institute (NCI) designated comprehensive cancer centers. The National Comprehensive Cancer Network provides detailed practice guidelines for the treatment of individual cancers. Guidelines are written by panels of experts drawn from the member institutions. The National Comprehensive Cancer Network Guidelines for the treatment of lung cancer do not recommend the use of the Guardant360 test due to decreased sensitivity (NCCN [National Comprehensive Cancer Network] Lung). This testing is only supported if there is insufficient tissue from the initial biopsy and if a solid tumor biopsy cannot be performed. The provided records did not document that a solid tumor biopsy was not possible. 

The National Comprehensive Cancer Network (NCCN) supports solid tumor biopsies when possible as the sensitivity for solid tumor biopsies for detecting mutations is greater than liquid biopsies and the sensitivity for detecting gene fusions is greater still (Wu; Mayo-de-Las-Casas).

The use of somatic 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). 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 (Jones). This study suggested that as many of 31% of "actionable" mutations in panels such as the FoundationOne test might be "false positive".

The use of next-generation sequencing panels for treatment selection for solid tumors was reviewed (Marrone). 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."

Reviews of the use of liquid biopsy assays for the management of lung cancer continue to consider this testing unproven (Hench; Rijavec).  

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