Download FoundationACT – Physician FAQs 1. What is cell

 FoundationACT – Physician FAQs 1. What is cell-­‐free DNA? Cell-­‐free DNA is DNA that circulates freely in the bloodstream. It is released from cells through apoptosis. 2. What is ctDNA? In a cancer patient, tumor cells that undergo apoptosis or necrosis also shed cell-­‐free DNA. The tumor derived cell-­‐free DNA is called circulating tumor DNA or ctDNA. 3. What are CTCs? Circulating tumor cells (CTCs) are intact tumor cells present in the peripheral bloodstream of patients with solid tumors. Whole cells (potential for analysis of DNA, RNA, protein localization & function) that have actively escaped or passively been shed into the bloodstream. 4. What is FoundationACT? FoundationACT (Assay for Circulating Tumor DNA) is a hybrid capture based next generation sequencing assay designed to interrogate specific coding regions across 34 genes, entire coding regions across 27 genes and select rearrangements across six genes within ctDNA. This assay is designed to identify all classes of alterations including base substitutions, insertions and deletions, copy number variations, and rearrangements. A complete gene list can be found in the technical specifications document. 5. What is FragTag? FragTag is a molecular barcoding technology where we use synthetic DNA barcodes to isolate unique ctDNA fragments 6. How is FoundationACT different from FoundationOne? FoundationOne is a tissue-­‐based comprehensive genomic profile for all solid tumors. For patients with inadequate tissue and repeat biopsy is not feasible, FoundationACT is a blood-­‐based assay that ensures that these patients have access to best-­‐in-­‐class genomic profiling. 7. What is the difference between FoundationACT and FoundationOne Heme? FoundationOne Heme is a comprehensive genomic profile for all hematological malignancies and sarcomas. FoundationACT is a blood-­‐based circulating tumor DNA assay for patients with solid tumors. When a tissue biopsy is not feasible, our liquid biopsy solution FoundationACT delivers reliable answers to uncover new treatment options for patients. 8. Who are the right patients for FoundationACT? FoundationACT was developed for patients with limited tissue access. As the ordering physician, this determination is within your purview, but we consider the following situations appropriate for testing with a liquid biopsy like FoundationACT: a. Insufficient or inadequate tissue from a recent biopsy b. Biopsy poses an unacceptable risk to the patient as assessed by treating physician c. Progression or recurrence is suspected and repeat biopsy is infeasible 9. What is the price of FoundationACT? The list price of FoundationACT is $5,800. 10. Is FoundationACT covered by insurance? Foundation Medicine bills the patient's insurance company for each test as the provider of service. Typically, it takes 60 to 90 days for the insurance company to respond to Foundation Medicine's claims. During this time the patient may receive an Explanation of Benefits; this is not a bill and will explain the coverage initially offered by the insurance company. If the insurance company denies coverage, Foundation Medicine works on behalf of the patient to attempt to obtain coverage and will assist in pursuing appeals on your behalf to minimize the financial burden when appropriate. We may also contact your office for assistance in the appeals process. 11. How long does it take for test results? Turn around time for FoundationACT is less than 14 days after we receive your patient’s sample. 12. How do I order FoundationACT? We have made the ordering process as simple as possible, so all your office needs to do is complete either a paper requisition form or do online ordering through FoundationICE portal. 13. How do I obtain test results? We will send the results via fax, and you may also access reports and links to additional information through FoundationICE, our online decision support platform for ordering physicians. If you are not a FoundationICE user, please contact your sales representative or call Client Services at (888) 988-­‐3639 to set up your FoundationICE account. 14. What are the specimen requirements? Two 10mL tubes of whole blood using the specimen collection tubes we provide. The samples can be stored and shipped at room temperature. 15. How do FoundationACT results compare to FoundationOne tissue-­‐based testing? Based on the validation data, FoundationACT assay results were 100% concordant with FoundationOne® tissue-­‐based testing. 16. Is FoundationACT a hotspot test? Liquid biopsy assays require more sequencing than tissue assays due to the trace amount of ctDNA found in blood. This is not unique to FoundationACT. FoundationACT was designed to capture all druggable alterations. In order to achieve this performance, we were highly efficient in allocating sequencing and decided to selectively cover some exons. 17. What is a failure due to low coverage? Tumors shed DNA into the blood stream at different rates due to a number of factors: tumor type, disease stage, patient age, etc. Some patients will not have detectable DNA with the FoundationACT assay. We can think of this as a TIFA/QNS that is not discovered until after sequencing. In these situations, we are unable to meet our specification of 5000x unique coverage. If we detect reportable alterations below this specification, we will issue a qualified report. In the event that we do not meet our coverage specification and do not identify any reportable variants, we will issue a failed report. We do this to avoid charging patients for results that are not likely beneficial to them and to avoid providing false negative results. This may be a more stringent standard than other liquid biopsy assays, but patient care is our highest priority at Foundation Medicine and we believe it is in the best interest of patient care to adhere by this policy. When a FoundationACT order fails we can repeat the test on another specimen, provide VUS information (if available), or seek out an alternative tissue specimen if available. For the best chance of success with FoundationACT testing, ensure patient selection is appropriate (late stage disease, solid malignancies) and full tubes of blood with proper patient identification information is provided. 18. Can FoundationACT results be used for clinical trial enrollment? Yes, unless inclusion criteria require a tissue-­‐based diagnosis 19. Can FoundationACT detect T790M? Yes, we interrogate the entire EGFR gene and can detect T790m and other resistance mutations with high sensitivity 20. Why did Roche recently launch a liquid biopsy cdx if they are a majority shareholder in FMI? Roche has updated their label for erlotinib to encompass specific EGFR mutations (exon 19, exon 21 substitution). This change requires availability of a companion diagnostic to support commercialization in certain markets, including the US, Australia and Canada. The test was launched due to a specific drug-­‐related requirement, not to capture a strategic opportunity in the diagnostics market.