Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis:  Metastatic adenocarcinoma of the lung.
Treatment:  Circulating tumor DNA test/liquid biopsy.

The insurer denied coverage for Circulating tumor DNA test/liquid biopsy.  The denial is upheld.

This patient is a female with metastatic adenocarcinoma of the lung initially presented with EGFR + Stage II lung cancer.  The patient was treated with surgery and adjuvant Pemetrexed and Cisplatin.  The patient had evidence of recurrent disease and a supraclavicular lymph node biopsy was positive for metastatic adenocarcinoma consistent with lung primary.  Foundation One testing was done on the lymph node biopsy and showed positive EGFR and negative PDL1.  Guardant360 was also done and was found to be positive for EGFR.

The Guardant360 is not FDA approved for use in this setting. The patient is not a good candidate for genetic testing (circulating tumor DNA test/liquid biopsy).  The patient had already had Foundation One testing done on the supraclavicular node and was found to be EGFR + and PDL1 negative. 

According to Gutierrez et al. (2017), "Current molecularly targeted therapies are not curative, and most patients will experience disease progression within 1 to 2 years. Newer targeted therapies designed to combat acquired mutations have been released, and the NCCN and European Society for Medical Oncology guidelines now recommend repeat genomic testing at progression to identify EGFR- and ALK-resistance targets. In our series, which largely predated these agents, repeat biopsies at progression during matched therapy were uncommon. Liquid biopsy approaches to detect acquired mutations or for identification of targets missed during the initial evaluation could be useful in this secondary resistance setting. In our series, 9 patients, including 6 patients receiving matched therapies for EGFR driver mutations, underwent liquid biopsy testing on progression. Targetable clonal EGFR T790M mutations were detected in 3 of the EGFR patients (50%), avoiding the need for repeat tissue biopsies. All 3 were treated with osimertinib, and 2 had a brief response (2 months). The third patient, who had developed brain metastases, had stable disease for > 1 year." 

In this case, Foundation One was the best available treatment for this patient at this time.  Tissue biopsy is the preferred method of testing, then liquid biopsy, if there are negatives in the tissue biopsy.

Per the NCCN guidelines, "Plasma Cell-Free/Circulating Tumor DNA Testing: Cell-Free/circulating tumor DNA testing should not be used in lieu of a histologic tissue diagnosis. Some laboratories offer testing for molecular alterations examining nucleic acids in peripheral circulation, most commonly in processed plasma (sometimes referred to as "liquid biopsy").  Studies have demonstrated cell-free tumor DNA testing to generally have very high specificity, but significantly compromise sensitivity with up to 30% false-negative rate.  Standards for analytical performance characteristics of cell-free tumor DNA have not been established, and in contrast to tissue-based testing, no guidelines exist regarding the recommended performance characteristics of the type of testing.  Cell-free tumor DNA testing can identify alterations that are unrelated to a lesion of interest, for example, clonal hematopoiesis of indeterminate potential (CHIP).  The use of cell-free/circulating tumor DNA testing can be considered in specific clinical circumstances, most notably: if a patient is medically unfit for invasive tissue sampling; in the initial diagnostic setting, if following pathologic confirmation of a NSCLC diagnosis there is insufficient material for molecular analysis, cell-free/circulating tumor DNA should be used only if follow-up tissue-based analysis is planned for all patients in which an oncogenic driver is not identified." 

Based on the review of the medical record and literature, requested treatment was not likely to be more beneficial than any of the standard treatments/procedures for this patient.

The carrier's denial of Circulating tumor DNA test/liquid biopsy; should be upheld.