FoundationAct- pro
The FoundationAct® genomic profile is one of several panels of tumor markers designed to give the oncologist an option of treating in a personalized manner directed to the specific markers that the cancer expresses. It is performed on blood rather than tissue as FoundationOne is. FoundationAct® is unique in that it is a pan-cancer profile – i.e., not restricted to one specific histology. It is a clinical diagnostic test based on sequencing from about 300 cancer related genes. This test includes all existing genes that are currently being tested for any type of cancer (i.e., BRCA 1&2, KRAS, BRAF, HER2, EGFR, etc.), but will include all exons and greater diagnostic sensitivity for mutations present in low abundance in heterogeneous samples which may suffer from mixed tumor and normal tissue, multiple clones, mixed aneuploidy etc. It will likely also contain the majority of known pharmacogenomic genes.
The manufacturer of FoundationAct® claims that it is highly accurate in identifying genomic alterations, including sensitivity greater than 99% for detection of base substitutions, 98% for detection of insertions and deletions, and greater than 95% for detection of copy number alterations, while maintaining greater than 99% specificity. Application of FoundationAct® to 2,221 clinical cases revealed clinically actionable alterations in 76% of tumor samples, three times the number of actionable alterations detected by other currently available diagnostic tests. Alterations are defined as clinically actionable if linked to an FDA approved targeted therapy in the tumor under study or another solid tumor, a known or suspected contraindication to a given therapy, or an open clinical trial for which the alteration confers patient eligibility.
Unfortunately, there needs to be a prospective study that shows that this approach is better than standard current regimens. Performing panels of multiple tests, some actionable and some not, for cancers and situation in which clear guidelines for treatment already exist, had not been proven to provide clinical guidance and is not currently recommended by any guidelines.
Therefore, and consistent with recognized professional standards of care, use of the FoundationAct® genomic profile for the purpose of assisting with clinical management decisions regarding cancer treatment is considered experimental/investigational at this time. The previous denial is hereby upheld.
REFERENCES[1]:
- Gwinn M, Grossniklaus DA, Yu W, Melillo S, Wulf A, Flome J, Dotson WD, Khoury MJ. Horizon scanning for new genomic tests. Genet Med. 2011 Feb; 13(2): 161-5.
- Rubinstein WS, Maglott DR, Lee JM, Kattman BL, Malheiro AJ, Ovetsky M. The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency. Nucleic Acids Res. 2013 Jan; 41 (Database issue): D925-35.
- Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013 Nov; 31(11): 1023-31.
- Gargis AS, Kalman L, Berry MW, Bick DP, Dimmock DP, Hambuch T. Assuring the quality of next-generation sequencing in clinical laboratory practice. Nat Biotechnol. 2012 Nov; 30(11): 1033-6.
- Ross JS, Ali SM, Wang K, Palmer G, Yelensky R, Lipson D. Comprehensive genomic profiling of epithelial ovarian cancer by next generation sequencing-based diagnostic assay reveals new routes to targeted therapies. Gynecol Oncol. 2013 Sep; 130(3): 554-9.
- Raman G, Avendano EE, Chen M. Update on Emerging Genetic Tests Currently Available for Clinical Use in Common Cancers. AHRG Technology Assessments. 2013 July. Agency for Healthcare Research and Quality.
[1] Although more than three years old, these references are consistent with current standard of practice.