Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Metastatic lung cancer
Treatment: Guardant 360 Test 

The health plan should not cover the Guardant 360 Test.

The patient is a male with metastatic non-small cell lung cancer (adenocarcinoma). 

Memorial Sloan Kettering performed a proprietary tumor mutation panel test on the tumor.

A Guardant360 liquid biopsy tumor mutation panel test was performed on his blood.This was the second Guardant360 test performed.

The patient had non-small cell lung cancer. A solid tumor mutation panel test was performed at the time of initial diagnosis. Guardant360 liquid biopsy tumor assays were performed twice.

The Guardant360 test is a next-generation sequencing (NGS) somatic mutation panel test that interrogates 68 genes including SNVs (single nucleotide variant), CNVs (copy number variant), indels (insertion-deletions), and rearrangements across more than 150,000 base pairs, aiding in treatment management (see https://www.guardanthealth.com/our-science/#). It is performed on cell free circulating DNA. 

The codes in question were billed for the Guardant360 test. 

The NCCN Guidelines for the treatment of lung cancer only support testing a tumor for driver mutations with a tumor mutation panel test once (NCCN Lung). Performing multiple tumor mutation panel tests, whether solid tumor or liquid biopsies, is not supported. 

The 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 2019; Mayo-de-Las-Casas 2018).

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 2015). The conclusion 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 enrollment 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 2015). This study suggested that as many as 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 2014). 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 mutation panel testing of tumors to select 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. The use of serial Guardant360 test results to guide the therapy of metastatic non-small cell lung cancer is of unproven benefit and is considered experimental/investigational. As the benefit of the testing is unproven, the testing can be withheld without affecting the patient's health adversely and would not be considered medically appropriate and should not be covered.

The Guardant 360 Test is not more likely to be more beneficial than any standard treatment or treatments for the insured's condition or disease.