Evolving at the Speed of Cancer: FoundationACT® Liquid Biopsy Data at ASCO 2017

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Comprehensive genomic profiling has opened the door to more precise medicines for many patients. Researchers and oncologists can identify genomic drivers of cancer growth or resistance to therapy, often with just a small tissue sample. But even if a tissue biopsy isn’t feasible, such as in patients with advanced disease or with tumors in difficult-to-access locations, doctors and patients can often still get genomic information to make better treatment decisions using a blood sample.

Today, blood-based genomic profiling, also known as liquid biopsy, can provide another option for detecting clinically significant alterations by interrogating circulating tumor DNA (ctDNA) that is shed from tumor cells into the bloodstream. At this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, we’re presenting new data supporting the ability of our FoundationACT liquid biopsy assay to identify potentially actionable genomic alterations across tumor types including lung, breast, gynecological, prostate and pancreatic cancers. This data advances our understanding of the capabilities of liquid biopsy in several indications and provides insight into the dynamic nature of cancer evolution.

For example, lung cancer patients often become resistant to multiple lines of targeted therapy due to the emergence of resistance mutations. Genomic profiling may help an oncologist understand why a patient stopped responding to their current treatment and inform selection of the next treatment. However, repeat tissue testing may not be feasible or safe, and liquid biopsy can serve as a non-invasive method to understand a patient’s disease progression. In a study of 1,552 non-small cell lung cancer (NSCLC) patients, FoundationACT detected several novel mechanisms of acquired resistance, including MET Y1230C and EGFR amplification after treatment with an ALK inhibitor. The study also found that certain patients undergoing treatment with an EGFR inhibitor develop acquired kinase fusions as resistance mechanisms. These findings provide clinical support for the ability of FoundationACT to detect diverse alteration types and inform next steps for treatment of individual NSCLC patients.

FoundationACT Identifies All Four Classes of Alterations

Metastatic breast cancer (mBC) is another type of cancer which is often characterized by tumor cell evolution during disease progression, which can limit the impact of a given treatment. At ASCO we are presenting data from a cohort of 328 mBC patients which showed that ctDNA in the blood was detected in 84% of cases, suggesting that liquid biopsy could be an important non-invasive tool to describe tumor cell evolution over the course of clinical care. Indeed, FoundationACT identified a diverse set of mutations in the ctDNA collected from these patients, including diverse ESR1 alterations which are thought to play a key role in acquired endocrine resistance in breast cancer.

FoundationACT is also demonstrating its ability to reveal important clinical insights for prostate cancer, a disease for which tissue may be difficult to obtain. Previous research has shown that prostate tumors with BRCA1/2 mutations may be sensitive to treatment with PARP inhibitors (PARPi), a promising type of treatment already approved in ovarian cancer and which recently received a breakthrough therapy designation for BRCA1/2 mutated prostate cancer. However, secondary reversion mutations can arise which may confer reduced sensitivity to PARPi. In another study of 1,911 patients with relapsed, refractory or metastatic prostate carcinoma, we show that both tissue and liquid biopsies were able to detect BRCA1/2 reversion mutations. These results support the ability of FoundationACT to detect mutations that may explain PARPi resistance in prostate cancer and complement tissue-based testing.

The future of cancer treatment relies on expanding our knowledge of cancer biology, including the genomic underpinnings of acquired resistance to therapy. At Foundation Medicine, we work steadily to build upon and enhance the ways we can help bring more genomic insights to oncologists, researchers, and patients. As we continue to evolve and innovate, liquid biopsy can help improve how we treat this disease by providing more options for more patients, and give us another tool to understand the genomic evolution of cancer.

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