FoundationOne is a comprehensive, next-generation sequencing (NGS) based test used to characterize all classes of molecular alterations (base substitutions, short insertions and deletions (‘indels’), copy number alterations and select rearrangements) across 287 cancer-related genes from routine formalin-fixed, paraffin-embedded (FFPE) clinical specimens.

The publication also describes clinical application of this assay across 2,221 consecutive patient cases.

This publication is the first to apply and extend the guidelines established by the next-generation sequencing: Standardization of Clinical Testing (Nex-StoCT) workgroup2 to validate a clinical sequencing-based assay for cancer, therefore setting the standard for validation of targeted NGS in cancer.

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.

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 US Food and Drug Administration 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.
Foundation Medicine president and CEO Michael J Pellini noted 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. 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," Pellini added.