Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: NSCLC
Issue under review: Guardant360 test

Determination:
The health plan should not cover the Guardant360 test.

The patient has metastatic nonsquamous non-small cell lung cancer. His tumor was tested for driver mutations, and was negative for driver mutations. A Guardant360 liquid biopsy somatic mutation test was performed on the patient's blood.

There is not enough outcome data available from controlled clinical trials published in the peer-reviewed literature to validate the safety and effectiveness of the use of the Guardant360 testing for management of non-small cell lung cancer. 

The National Comprehensive Cancer Network (NCCN; URL: www.nccn.org) is an organization whose members are drawn from the nation's NCI (National Cancer Institute) designated comprehensive cancer centers. NCCN provides detailed practice guidelines for the treatment of individual cancers. Guidelines are written by panels of experts drawn from the member institutions. The NCCN Guidelines for the treatment of lung cancer do not recommend any mutation testing at the time of progression in patients whose cancers have been previously tested for driver mutations (NCCN Guidelines Version 5.2019, Non-Small Cell Lung Cancer). 

The standard of care in the United States does not yet include selecting chemotherapy for cancer based on the genomic profile of circulating cell free DNA. 

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 vs 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; SHIVA investigators. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015 Oct;16(13):1324-34). 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."

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. Multi-marker Solid Tumor Panels Using Next-generation Sequencing to Direct Molecularly Targeted Therapies. PLoS Curr. 2014 May 27;6. pii: ecurrents.eogt.aa5415d435fc886145bd7137a280a971. doi: 10.1371/currents.eogt.aa5415d435fc886145bd7137a280a971). 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 such somatic mutation sequencing panels 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.