Frequently Asked Questions

A genomic alteration (or mutation) is a change in the DNA sequence that makes up a gene and can affect the way a cell functions. The genome comprises the entirety of the nuclear DNA, and whilst genomic alterations are a normal part of life, most won’t have a negative effect on our health. But some alterations lead to diseases, including cancer. Cancers are caused by alterations within several hundred specific genes that are found in the cells of our bodies. When changes occur in these genes, cells can grow in an abnormal fashion, causing cancerous tumours to form. These tumours may become metastatic and spread throughout the body.

Targeted therapies target specific underlying genomic alterations that are contributing to tumour growth. By attacking the cancer and sparing the surrounding tissue, targeted therapies can be more effective and have fewer and less pronounced side effects than traditional chemotherapies. Since there are hundreds of genes that can have alterations in cancer, and many possible alterations in each gene, the number and combination of genomic alterations make each person’s cancer unique. Immunotherapies harness the body’s own immune system to attack cancer cells. Targeted therapies and immunotherapies may be available as Food and Drug Administration (FDA)-approved or European Medicines Agency (EMA)-approved therapies or they may be available as part of a clinical trial.

If you decide to order a comprehensive genomic profiling (CGP) test for your patient, you would start the process by submitting a Test Order Form. Foundation Medicine performs a type of biomarker testing called CGP. Once you submit the Order Form to us along with the pathology report, billing information and any other attached paperwork, we will then contact the hospital that has the tumour sample so it can be sent to us for testing. We will analyse the sample to identify any genomic alterations that may be driving the cancer. We will then issue a report back to you that lists the genomic alterations, additional biomarkers, and the targeted therapies, immunotherapies, or clinical trials that you and your patient may consider for the next stage in your treatment.

FoundationOne® CDx and FoundationOne® Liquid are suitable for most patients with malignant solid tumour cancers. These tests are most frequently used in patients with advanced, recurrent and / or metastatic cancers who have exhausted standard of care treatment options. The FoundationOne® CDx and FoundationOne® Liquid reports reveal clinically relevant alterations in tumour DNA that are associated with the effect of targeted cancer treatments either documented in the existing clinical literature or that are being explored in clinical studies.

The ordering Oncologist will receive a report approximately 11 to 14 days after Foundation Medicine receives a satisfactory tissue sample.

We will send the results via your Foundation Online account and/or by secure email.

You are solely responsible for any and all action(s) undertaken as a result of the information provided in the FoundationOne® CDx or FoundationOne® Liquid report and Roche does not seek to recommend any particular medication(s) referred therein. It is your responsibility to evaluate and interpret the information provided in the report, along with all other available clinical information regarding your patient, in order to determine the best treatment decision(s) in your own independent medical judgment, and as far as possible in collaboration with other healthcare professionals involved in the care of your patient.

No, this service is not designed to predict response to chemotherapy or recurrence. The service helps match the genomic alterations present in a tumour with specific targeted therapies or clinical trials.

FoundationOne® CDx and FoundationOne® Liquid may identify an "actionable" mutation(s) helping:

1. Identify an EMA-approved therapy for the patient's tumour type and shown to target one or more of the genomic alterations found by the service,*

2. Identify an EMA-approved therapy in another tumour type and shown to target one or more of the genomic alterations found by the service, or*

3. Identify clinical trials of a licensed or experimental treatment which may work by targeting an alteration found by the service or a relevant pathway

*The FoundationOne® Liquid report may also include therapies approved by the FDA.

FoundationOne® CDx and FoundationOne® Liquid are designed to profile any type of tumour regardless of where it is found in the body or how advanced the cancer. However, the services are generally used for more advanced disease or disease that has spread.

The results will provide information on any acquired genomic alterations¹ found in a patient's tumour but are not intended to provide information on inherited genetic alterations. It is important to remember that only 5–10 percent of cancers are caused by hereditary alterations. However, since these alterations can be inherited by multiple family members and passed down from generation to generation, information about inherited alterations affects entire families, raising personal and ethical considerations that factor into the decision to receive that information. FoundationOne® CDx is not a service for inherited alterations.

_References

_{1. https://www.cancer.gov/about-cancer/causes-prevention/genetics (last accessed November 2019)}

There is a possibility that in some cases, FoundationOne® CDx or FoundationOne® Liquid results don't identify an actionable genomic alteration, meaning there are no approved treatments or therapies in clinical trials that have been shown to be effective against the alterations found in a patient’s tumour. Additionally, there may be obstacles to obtaining therapy in cases where the service finds actionable alterations. For example, if the therapy has been approved in a different tumour type, there may be no reimbursement for the cost of that treatment for an unapproved tumour type. It is also possible that a patient may not be eligible for, or able to enrol in an ongoing clinical trial of a therapy targeted against an alteration found by the service.

It is important to understand that while the service often provides valuable information to help healthcare professionals make the best possible decisions about treatment, there is no guarantee that the treatment identified will work for the patient. While significant progress has been made in treatments targeting the underlying genomic alterations that cause cancer, cancer is a complex disease driven by multiple factors, no therapy is 100 percent effective and responses to therapies vary.

FoundationOne® CDx is a tissue-based comprehensive genomic profiling (CGP) service for all solid tumours. FoundationOne® CDx detects the four main classes of genomic alterations (base substitutions, insertions or deletions, copy number alterations and gene rearrangements) in 324 cancer-relevant genes, as well as reporting tumour mutational burden (TMB) and microsatellite instability (MSI)-High status.

• Updated gene list: FoundationOne® CDx has an updated gene list to capture the most clinically relevant genomic alterations. FoundationOne® CDx interrogates 324 known cancer relevant genes vs 315 known cancer relevant genes (FoundationOne®)

• Simplified report: FoundationOne® CDx has a simplified report format. Key clinical information is captured on the first page of the report. This will include any EMA-approved therapies for the identified tumour type and EMA- approved therapies in another tumour type alongside potential clinical trials

• Assessment of the four main classes of genomic alterations

• Assessment of Tumour Mutational Burden (TMB) and Microsatellite Instability (MSI)

• Cost

• Tissue requirements

• Turnaround time (11–14 days – upon receipt of a viable sample in the Foundation Medicine Laboratories)

FoundationOne® CDx requires 40 \0x03BCm of FFPE tissue, of which a minimum of 20% should be of malignant origin, however 30% is optimal, on 10 unstained slides or from a block reviewed and approved by a pathologist as the most representative block for the patient diagnosis. All solid tumour types are acceptable. Foundation Medicine is able to process any clinical sample that meets these guidelines. Should your sample be insufficient or unsatisfactory you will be notified as soon as possible following receipt.

FoundationOne^® CDx Specimen requirements

A recent sample of a patient’s tumour is preferred as genomic alterations are known to change over time and with treatment. The service can be run on a tissue sample from an earlier biopsy of either the primary tumour or cancer cells that have spread to other parts of the body. If there is not enough tissue remaining from an earlier biopsy to run the service an additional biopsy may need to be collected. It may be required to take a new biopsy to get a more recent sample.

FoundationOne® Liquid is an additional CGP service for patients with solid tumours. FoundationOne® Liquid detects the four main classes of genomic alterations (base substitutions, insertions or deletions, copy number alterations and gene rearrangements) in 70 cancer-relevant genes, as well as reporting MSI‑High status.

FoundationOne® Liquid uses circulating tumour (ct)DNA and provides an alternative biopsy service for patients that are not suitable candidates for the tissue-based FoundationOne® CDx service. ctDNA is released from tumour tissue and circulates in the blood, this can be examined following ctDNA extraction using a blood draw. ctDNA is highly fragmented, occurs in very low amount and varies between both tumour types and individual patients. This method may be an appropriate technique when:

• Insufficient or inadequate tissue from a recent biopsy can be obtained

• The tumour is “difficult to biopsy”

• Biopsy poses an unacceptable risk to the patient or is contraindicated

• Progression or recurrence are suspected and repeat biopsy is infeasible

The FoundationOne® Liquid output is a US-based report, which may include therapies approved by the FDA, but not through the EMA at the time of testing – this is in contrast to the FoundationOne® CDx report, which may include therapies approved through a centralised EU procedure or a national procedure in an EU Member State.

FoundationACT® is a prior version of FoundationOne® Liquid, which has been analytically validated.

FoundationOne® Liquid has an updated gene list to capture the most clinically relevant genomic alterations. FoundationOne® Liquid interrogates 70 known cancer-relevant genes vs 62 known cancer-relevant genes (FoundationACT®).

FoundationOne® Liquid requires two tubes of peripheral whole blood (8.5 mL per tube), filled to the marked level. Each tube should be mixed by gentle inversion 8 to 10 times – inaccurate or delayed mixing may result in inaccurate test results (one inversion is 180 degrees). All solid tumour types are acceptable. Foundation Medicine is able to process any clinical sample that meets these guidelines. Should your sample be insufficient or unsatisfactory you will be notified as soon as possible following receipt.