Advances in the understanding of the molecular basis of cancer

Over the past two decades have led to the development of therapies approved to treat cancers harboring specific genomic biomarkers.^1-2 As a result, precision oncology, the use of molecular biomarkers to aid in the diagnosis, prognosis or treatment of cancer, is now possible for multiple types of tumors.³

Additionally, improvements in next-generation sequencing (NGS), a technology that enables massively parallel DNA sequencing, have led to the development of multi-gene panels. Gene panels can include only the most critical, clinically relevant portions of genes or can be comprehensive, containing coding and non-coding regions of genes, and even gene fusion detection.⁴

Comprehensive Genomic Profiling (CGP)

Refers to NGS-based molecular assays that provide additional insight beyond individual gene hotspots; CGP assays can help characterize the underlying mechanisms of disease and may identify genomically-matched treatment options such as a targeted therapy or immunotherapy. CGP typically involves sequencing of entire exonic regions of genes of interest (within a comprehensive gene panel or whole exome sequencing) and may also include selected intronic regions.

CGP can detect multiple types of molecular alterations (i.e., single nucleotide variants (SNVs), small and large insertion and deletion mutations (INDELs), copy number alterations (CNAs), structural variants (SVs) and splice-site variants) in a single assay, and may be used to calculate microsatellite instability (MSI) status and tumor mutational burden (TMB).^4-5

In addition to guiding treatment selection, CGP may optimize clinical management by excluding the use of ineffective therapies,^6-8 determining eligibility for clinical trials for genomically-matched and biomarker- driven therapies^7,9 and by informing diagnosis and/or prognosis.^10-13 Given the rapid evolution of the field of precision oncology, and the need to efficiently identify an optimal treatment plan, there is increasing support for an expanded, broad or comprehensive approach to molecular or genomic profiling for a growing number of advanced solid tumors.^{3, 14-21}

Necessary Briumvi

Although tissue-based testing is considered the gold-standard approach to molecular testing, tissue may not always be available or feasible to obtain. When comparing tissue and liquid biopsy, there are considerations that may factor into clinical decision-making such as: when the tissue specimen is exhausted from prior testing, patient preference to avoid (or contraindication for) a repeat invasive biopsy, patient progression on therapy, and lack of an available biopsy site to obtain an adequate sample for testing.

A number of NCCN Guidelines recommend liquid biopsy (plasma) testing in certain clinical circumstances.^{14-15, 18-20, 22-25} Because studies have shown substantial concordance between cell free DNA (cfDNA)-based testing and tumor testing, in patients without tissue-based genomic test results, treatment may be based on actionable alterations identified in cfDNA.³

FoundationOne^®CDx is a qualitative next-generation sequencing based in vitro diagnostic test that uses targeted high throughput hybridization-based capture technology for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin- embedded (FFPE) tumor tissue specimens.²⁶

FoundationOne^® Liquid CDx is a qualitative next generation sequencing based in vitro diagnostic test that uses targeted high throughput hybridization-based capture technology to detect and report substitutions, insertions and deletions (indels) in 311 genes, rearrangements in four (4) genes and copy number alterations in three (3) genes. FoundationOne Liquid CDx utilizes circulating cell-free DNA (cfDNA) isolated from plasma derived from anti-coagulated peripheral whole blood of cancer patients collected in FoundationOne Liquid CDx cfDNA blood collection tubes included in the FoundationOne Liquid CDx Blood Sample Collection Kit.²⁷

For additional information, refer to U.S. Food & Drug Administration List of Cleared or Approved Companion Diagnostic Devices.
List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools) | FDA

NOTE: Genetic and molecular diagnostic testing requests for members of Harvard Pilgrim Health Care Commercial and Tufts Health Public Plans are managed by Carelon Medical Benefits Management (Carelon). Ordering providers may submit authorization review requests online 24/7 at www.providerportal.com or by phone by calling Carelon toll-free at: 833-342-1255 (Mon.– Fri., 8 a.m.– 5 p.m. EST).

Clinical Guideline Coverage Criteria

FoundationOneCDx or FoundationOneLiquidCDx may be authorized when all the following criteria are met:

1. The Member has either recurrent, relapsed, refractory, metastatic, or any stage III or stage IV cancer; and
2. The Member has decided to seek further cancer treatment.

Limitations

• Tufts Health Plan will not cover both FoundationOneCDx and FoundationOneLiquidCDx in the same member for same primary cancer diagnosis.