Clinical Application of the FoundationOne CDx Assay to Therapeutic Decision-Making for Patients with Advanced Solid Tumors

Abstract

Background Implementation of personalized medicine requires the accessibility of tumor molecular profiling in order to allow prioritization of appropriate targeted therapies for individual patients. Our aim was to study the role of comprehensive genomic profiling assays that may inform treatment recommendations for patients with solid tumors. Materials and Methods We performed a prospective study to evaluate the feasibility of application of the FoundationOne CDx panel—which detects substitutions, insertions and deletions, and copy number alterations in 324 genes, select gene rearrangements, and genomic signatures including microsatellite instability and tumor mutation burden (TMB)—to patients with advanced or recurrent solid tumors before its approval in Japan. Results A total of 181 samples were processed for genomic testing between September 2018 and June 2019, with data being successfully obtained for 175 of these samples, yielding a success rate of 96.7%. The median turnaround time was 41 days (range, 21–126 days). The most common known or likely pathogenic variants were TP53 mutations (n = 113), PIK3CA mutations (n = 33), APC mutations (n = 32), and KRAS mutations (n = 29). Among the 153 patients assessed for TMB, the median TMB was 4 mutations/Mb, and tumors with a high TMB (≥10 mutations/Mb) were more prevalent for lung cancer (11/32) than for other solid tumor types (9/121, Fisher's exact test p < .01). No clear trend toward increased efficacy for immune checkpoint inhibitor (ICI) monotherapy or ICI combination chemotherapy in patients with a high programmed cell death–ligand 1 tumor proportion score or a high TMB was apparent. Among the 174 patients found to harbor known or likely pathogenic actionable alterations, 24 individuals (14%) received matched targeted therapy. Conclusion The FoundationOne CDx assay was performed with formalin‐fixed, paraffin‐embedded tumor specimens with a success rate of >95%. Such testing may inform the matching of patients with cancer with investigational or approved targeted drugs. Implications for Practice This prospective cohort study was initiated to investigate the feasibility and utility of clinical application of FoundationOne CDx. A total of 181 samples were processed for genomic testing between September 2018 and June 2019, with data being successfully obtained for 175 of these samples, yielding a success rate of 96.7%, and 24 individuals (14%) received matched targeted therapy.

The Impact of Foundation Medicine Testing on Cancer Patients: A Single Academic Centre Experience

“…In our study, the most common mutation was also TP53 (47%), but the second most common mutation identified in our study was CDKN2A (29%). Our study showed a median age of patients to be 56 years, which is similar to a study on hematological cancers sent for comprehensive genetic profiling, whom had a mean age of 54 years ( 10 ) but slightly dissimilar to the median age of 62 years found in patients with advanced solid tumors sent for FoundationOne CDx panel ( 18 ).…”

“…A study on rare and refractory cancers, found that the most common mutations identified were TP53 (46%), followed by RAS/RAF/APK(45%) ( 8 ). A study on advanced solid tumors using FoundationOne CDx panel found TP53 (65%) followed by PIK3CA (19%) were the most common mutation identified ( 18 ). A final study using FoundationOne CDx testing found the most common mutations identified were KRAS (94%) followed by TP53 (76%) ( 19 ).…”

Multi-Gene Testing Overview with a Clinical Perspective in Metastatic Triple-Negative Breast Cancer

“…Though there are some differences across different panels in terms of the number of genes included and genetic alterations evaluated, they all include well-known high-penetrance genes, as well as moderate-and low-penetrance genes and variants of unknown significance (VUS) [19]. The only two panels approved by FDA as companion diagnostic for solid tumors are FoundationOne CDx (324 genes) [20] and MSK-IMPACT (468 genes) [21], which are performed in CLIA (Clinical Laboratory Improvement Amendments)-certified laboratories. Nonetheless, there are many targeted panels that clinicians can order from certified facilities like Caris Life Science (592 genes) by Caris Molecular Intelligence, as well as commercially available panels to test in research laboratories like Thermo Fisher's Oncomine Cancer Gene Mutation Panel v2 assay (143 genes), Oncomine Comprehensive Panel_v3 DNA (161 Genes), Oncomine Focus Assay DNA (52 Genes), Illumina's TruSight Oncology 500 (523 genes), TruSight Tumor 170 (170 genes), and QIAGEN's QIAseq Targeted DNA Panels just to name some of the most commonly advertised.…”

Current Advances in Clinical Application of Liquid Biopsy

“…Recent developments in DNA extraction methods and optimisation improve assay performance [42,43]. In fact NGS solutions have been achieving regulatory approval such like Oncomine Dx (ThermoFisher Scientific) for targeted therapies in non-small cell lung carcinoma (NSCLC) [44]; Praxis (Illumina) characterising 56 KRAS/NRAS mutations for colorectal cancer companion diagnostics (CDx); Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), the first U.S. Food & Drug Administration (FDA) approved tissue profiling test that detecting aberrations across 341 cancer genes for solid cancer tissue diagnostics but not prescriptive for any specific therapeutic product [45]; and FoundationOne CDx which is the first FDA-approved broad CDx test that is clinically and analytically validated for all solid tumours for therapeutic indication and has a success rate of >95% on FFPE [46].…”