Appeal type: Experimental/Investigational
Decision: Upheld

Reviewer # 2:

This is a female patient with a diagnosis of left lung adenocarcinoma that was diagnosed a few years prior to presentation. The patient was treated with EGFR tyrosine kinase inhibitor. A Guardant360 assay was performed which showed no gene alterations. There was recommendation for biopsy versus resection; the patient and family declined.

The scientific evidence in reviewed literature does not support improvement in health outcomes. There are no high-grade randomized prospective controlled trials showing that the use of this testing to direct therapy in non-small cell lung cancer improves health outcomes.

The patient has non-small cell lung cancer and the cancer stage is not definitively documented. It is unclear if the patient has metastatic disease. Guardant360 assay was done to assess for development of molecular mutations. The use of Guardant360 has not been shown to improve outcomes in the setting.

There is limited high-grade clinical trial data that shows the efficacy of the guardant 360 assay for the treatment of lung cancer. Schwaederle, et al. performed Guardant360 testing in 88 lung cancer patients and found 82% with at least one genomic alteration of which 75% were potentially actionable. At the moment though, there are no high-grade trials such as randomized controlled trials which show that the use of this information to direct patient care results in improvement in health outcomes.

Although NCCN guidelines Non-small Cell Lung Cancer 1.2020 states that for stage IV lung cancer, molecular testing with EGFR, ALK, BRAF, PDL1 should be considered as part of a broad molecular profiling, It should be noted that the purpose would be to identify driver mutations for which drugs have been noted to be useful in other malignancies and for which patients would be counseled regarding the availability of clinical trials. The utility of this information is debatable as again, the targeted agents advised by such results would have not been conclusively proven to be useful for the diagnosis of non-small cell lung cancer. There is also no indication which specific molecular profiling would be appropriate considering that there are several available types including tumor tissue profiling versus liquid biopsy profiling. The NCCN guidelines indicate that the use of cell-free tumor DNA testing to have significantly compromised sensitivity with high false negative rates, can identify alterations that are unrelated to a lesion of interest, and the standards for analytical performance have not been established for this type of test. 

Similarly, ASCO guidelines (2016) also recommend testing for EGFR, ALK, and ROS1 as molecular testing for metastatic non-small cell lung cancer.  They do not recommend specifically multi gene panels using cell free DNA. 

The Guardant360 assay is not the best available treatment for the patient at this time.  The best available treatment the patient at this time includes molecular testing based on testing done on tumor tissue. There is no clear indication that the member previously was diagnosed with an EGFR mutation despite the use of a tyrosine kinase inhibitor.

The carrier's denial of Genetic Testing 81201, 81272, 81173, 81321, 81210, 81275, 81310, 81120, 81235, 81276, 81311, 81121, 81270, 81293, 81314, 81400, 81401, 81402, 81403, 81404, 81405, 81406 and 81407 (Guardant 360 blood test) should be upheld.