Foundation Medicine Reports Validation of FoundationOne Assay

By Bio-IT World Staff

October 21, 2013 | Foundation Medicine has announced findings from a 24-month, multi-institution collaboration demonstrating the analytic validation of its FoundationOne cancer genomics assay. The results were published in the online edition of Nature Biotechnology.

FoundationOne characterizes all classes of molecular alterations (base substitutions, short insertions and deletions, copy number alterations and select rearrangements) across 287 cancer-related genes from routine formalin-fixed, paraffin-embedded (FFPE) clinical specimens. The publication describes clinical application of this assay across 2,221 consecutive patient cases.

The publication applied and extend the guidelines established by the Next-Generation Sequencing: Standardization of Clinical Testing (Nex-StoCT) workgroup to validate a clinical sequencing-based assay for cancer, therefore setting the standard for validation of targeted NGS in cancer.

"Clinical cancer care is undergoing a fundamental shift toward treating patients based on the specific molecular drivers of their disease, and a sequencing-based diagnostic assay that comprehensively and accurately characterizes the genomic alterations occurring within an individual's tumor is essential for the implementation of this therapeutic strategy," said Lajos Pusztai, M.D., co-director of the Cancer Genetics and Genomics Research Program at Yale Cancer Center and co-author of the study in a statement. "This study is instrumental in establishing the technical validity of next-generation sequencing in the clinic and enables the practice of precision medicine wherein the molecular characterization of a patient's tumor informs the patient's individual treatment."

Foundation Medicine assessed the accuracy and precision of FoundationOne using reference samples of pooled cell lines and hundreds of clinical cancer specimens with diagnostic testing results generated by established clinical assays. FoundationOne was found to be 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, reports the company.

Application of FoundationOne 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.

"FoundationOne was proven to have the sensitivity and specificity required for routine clinical practice, and it identified more than three times the clinically actionable alterations that are identifiable using a collection of six commercially available and commonly used diagnostic tests, including the other most common NGS-based tests. This comprehensive approach directly translates into more treatment options for patients," said Michael J. Pellini, M.D., president and chief executive officer of Foundation Medicine. "We believe this study establishes the standard for analytic performance that is required for patients with cancer to benefit from the clinical application of next-generation sequencing of their tumors."

Frampton, G.M. et al. Validation and clinical application of a cancer genomic profiling test using next-generation sequencing. Nature Biotechnology, 2013; DOI: 10.1038/NBT.2696.

Gargis, A.S. et al. Assuring the quality of next-generation sequencing in clinical laboratory practice. Nature Biotechnology 30, 1033-1036 (2012).