Frequently asked questions

PATIENT AND SAMPLE ELIGIBILITY

1. What is the patient eligibility for this program?

All patients with solid tumours that are metastatic or when surgical resection is likely to result in severe morbidity, and for whom no satisfactory treatment options are available meet the criteria to be tested.

2. I have many patients to test. Which patients should be tested?

Considering the above eligibility criteria, testing for NTRK gene fusions should be performed for patients with the following tumour types:

  • Tumour types known to frequently harbour NTRK gene fusions (i.e. infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analogue secretory carcinoma, and secretory breast cancer)1
  • Commonly diagnosed tumour types (e.g. lung cancer and colorectal cancer) known to be negative for other oncogenic alterations through exclusionary testing
  • CRC patients with MSI-H/dMMR status2-4
  • Thyroid cancer, salivary cancer, and sarcoma patients

References: 1. Cocco E, et al. NTRK  fusion-positive cancers and TRK inhibitor therapy. Nature Reviews Clinical Oncology 2018;15:731–47. 2. Pietrantonio F, et al. ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer. J Natl Cancer Inst 2017;109(12). 3. Chou A, et al. NTRK gene rearrangements are highly enriched in MLH1/PMS2 deficient, BRAF wild-type colorectal carcinomas—a study of 4569 cases. Mod Pathol 2019, doi.org/10.1038/s41379-019-0417-3. 4. Jiao X, et al. Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients. ESMO 2019. Abstract no. 485P.

3. How do I access FastTRK and which requisition form do I use?

  • 1 Click here to download the appropriate requisition form, you will need to indicate your hospital name. (The testing lab option will change based on your geographical location). Please use the appropriate requisition form.
  • 2 Please ensure that the patient eligibility and consent sections are completed.
  • 3 Coordinate with your local pathology department to ship a copy of the completed requisition form and required patient sample to the testing lab. Please refer to sample details section for more information.
  • 4 Shipping costs associated with mailing samples to and from originating hospital to centralized testing labs is covered under the Fast TRK program. Please review to shipping details section as outlined on the requisition form.
  • 5 Turn-around time for the testing report will be anywhere from 2–15 business days depending on the outcome of the test(s).

4. Can you clarify that patients with lung cancer and colorectal cancer would be eligible for testing under this program?

Currently, the Fast TRK (NTRK  fusion clinical testing program) is available for all patients with solid tumours that are metastatic or when surgical resection is likely to result in severe morbidity, and for whom no satisfactory treatment options are available. Specifically, for commonly diagnosed tumour types such as lung cancer and colorectal cancer known to be negative for other oncogenic alterations through exclusionary testing would be appropriate candidates for this testing program. Additionally, colorectal cancer patients with MSI-H/dMMR status,1–3 have been associated as a patient segment enriched for NTRK gene fusions.

References: 1. Pietrantonio F, et al. ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer. J Natl Cancer Inst 2017;109(12). 2. Chou A, et al. NTRK gene rearrangements are highly enriched in MLH1/PMS2 deficient, BRAF wild-type colorectal carcinomas—a study of 4569 cases. Mod Pathol 2019, doi.org/10.1038/s41379-019-0417-3. 3. Jiao X, et al. Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients. ESMO 2019. Abstract no. 485P.

5. Are patients known to have other genomic alterations (i.e. KRAS) eligible for testing?

As per the exclusionary testing guidelines in the Fast TRK information sheet, the absence of other genomic alterations (such as KRAS) are not mandatory to qualify for the Bayer funded NTRK  fusion testing program. However, the disease will still need to meet the primary criteria of being metastatic or when surgical resection is likely to result in severe morbidity, and for whom no satisfactory treatment options are available.

Dr. Jiao and groups presented at ESMO 2019 in Barcelona on the co-occurrence of NTRK  fusions with other genomic biomarkers in cancer patients.1 This retrospective study included patients with cancer from a de-identified Flatiron Health–Foundation Medicine Clinico-Genomic Database (CGDB; Version November 2018) whose tumours had been profiled by comprehensive genomic profiling (CGP) between January 2011 and July 2018. During this period, FoundationOne used an evolving set of baits for the detection of NTRK 1, 2 and 3. All bait sets had complete coverage of all NTRK 1, 2 and 3 coding exons; NTRK 1, NTRK 2 and ETV6 intron coverage varied by assay. In the study, data from 15,971 evaluable tumor samples across 18 distinct histologies were evaluated. Co-occurrence of the biomarkers ALK, BRAF, ERBB2, EGFR, ROS 1 and KRAS was uncommon in patients with NTRK gene fusions, suggesting that NTRK  gene fusions are primary oncogenic drivers in tumours that harbour them. Additionally based on this data, the co-occurrence of NTRK  fusions with KRAS alternations although uncommon it was seen in 3/29 NTRK gene fusion positive samples (2 colorectal and 1 lung cancers) in this particular study. This highlights the importance of NTRK gene fusions as actionable drug targets and the need for NTRK gene fusion testing across different solid tumours.

References: 1. Jiao X, et al. Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients. ESMO 2019. Abstract no. 485P.

6. What is the most efficient way to screen for NTRK fusions among CRC patients?

Available data from three independent studies indicate that NTRK  fusions in CRC are highly enriched in MSI-H/dMMR/BRAF  wild-type patients (MSI-H/dMMR status was determined in all three available studies, BRAF V600E status was determined in two of three studies). In their study, Pietrantonio et al, demonstrated that 77% of identified CRC patients with an NTRK  fusion were also MSI-H (10/13) and all were BRAF  wild-type (13/13, patients with various NTRK 1/3 fusion partners).1 In a distinct study, Chou et al, found that 89% of NTRK  fusion positive CRC cases identified (8/9 NTRK  fusion positive CRC patients identified from 4569 consecutive cases) were dMMR (MLH1/PMS2 loss) and 100% lacked BRAF V600E mutation (9/9).2 In a separate retrospective analysis of 29 NTRK  fusion cancer patients published at ESMO 2019, 75% of NTRK  fusion positive CRC cases for which MSI status was available (3/4 from a total of 7 CRC with NTRK  fusions) were shown to be MSI-H.3 Therefore, while the identification of all CRC patients with NTRK  fusions would require systematic NGS detection, taken together, available data however indicate that NTRK  detection performed in MSI-H/BRAFV600E double negative or MLH1/PMS2/BRAF V600E triple negative (less than 4% of all CRCs) could enable the identification of the majority of NTRK  fusion positive CRC patients. This summary is up to date as of December 12, 2019.

References: 1. Pietrantonio F, et al. ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer. J Natl Cancer Inst 2017;109(12). 2. Chou A, et al. NTRK gene rearrangements are highly enriched in MLH1/PMS2 deficient, BRAF wild-type colorectal carcinomas—a study of 4569 cases. Mod Pathol 2019, doi.org/10.1038/s41379-019-0417-3. 3. Jiao X, et al. Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients. ESMO 2019. Abstract no. 485P.

7. What if my patient is diagnosed with an NTRK gene fusion?

If consent has been provided in the requisition form, Bayer Medical Affairs can be in contact with the clinician regarding additional medical information.

SAMPLE PROCESSING AND TESTING FLOW

8. As an initial step, can I send in just enough slides to perform a pan-TRK IHC?

Yes, if specimen material is limited, you can send enough material to run a pan-TRK IHC screening first. If this test is positive for TRK protein, the IHC test report will indicate that and you can send in additional slides to confirm the presence of NTRK  gene fusion by NGS. A new requisition form for a new submission will be required. Please review the requisition form for specific details on sample requirements.

9. For lung and colorectal cancer patients, do we need to provide documentation that shows exclusion of other known oncogenic drivers?

Testing for NTRK  gene fusions should be performed for patients with commonly diagnosed tumour types (e.g. lung cancer and colorectal cancer) known to be negative for other oncogenic alterations through exclusionary testing. However, documentation of test results is not a “prerequisite” for Fast TRK. Please note, that Fast TRK is a complimentary clinical testing program for the diagnosis of NTRK  gene fusions where the primary reason for testing is suspicion of an NTRK  gene fusion.

10. Who covers shipping costs of tumour sample?

The shipping costs for sending the patient sample to and from a Fast TRK lab will be covered by Bayer. Please contact Bayer to receive the courier account number and information.

11. Our lab routinely screens for NTRK gene fusion by IHC. Can we just send the samples that are pan-TRK IHC positive to Fast TRK for NGS confirmation or does Bayer require both IHC and NGS to be performed in the Fast TRK program?

Yes, samples that are stained positive for TRK protein by a pan-TRK IHC assay can be sent to Fast TRK for immediate testing by NGS. The Fast TRK program does not have a requirement for exclusive IHC testing by its third-party service provider(s). Please indicate this in the section on the requisition form “Prior Testing” that this sample was found to be positive for TRK protein. A pathology report indicating the positive IHC test results for TRK protein over-expression obtained by a certified academic pathology lab should accompany the requisition form and shipped with the patient sample.

12. Is there a protocol/ algorithm for which test will be done for which sample? IHC vs NGS?

Tumour types known to frequently harbour NTRK  gene fusions (i.e. infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analogue secretory carcinoma, and secretory breast cancer) or where native TRK protein is endogenously found such as neuronal tissues will undergo next generation sequencing (NGS) upfront. However, testing for commonly diagnosed tumour types (e.g. lung cancer, thyroid, soft tissue sarcomas, colorectal cancer, etc.) that are known to harbour lower frequencies for NTRK  fusions will be initiated with a pan-TRK IHC screen to detect for TRK protein over-expression. Only positive samples from IHC will proceed to molecular testing by next generation sequencing.

13. How do I work with the pathology department to get the patient sample? Does the Fast TRK program help to coordinate this?

The Fast TRK testing labs will not perform any coordination to procure the samples from the requesting institutions. You must coordinate the collection of the specimen with your pathology department. If the patient’s specimen is at another hospital, the requesting physician should co-ordinate with the pathology department at that hospital to complete the form, send it to that hospital (fax/email – as per privacy requirements for those institutions). The Pathology Department at the indicated hospital should include a copy of the completed requisition form with the patient sample prior to shipping to the service lab for testing.

14. Who can initiate the request for NTRK  gene fusion testing? Does it need to be an oncologist?

Yes, in most cases this testing request would be initiated by oncologists. However, if your institution has reflex testing for specific cancer types or stages, it is possible for pathologists to request NTRK  fusion testing. This could be relevant for tumour types known to frequently harbour NTRK  gene fusions (i.e. infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analogue secretory carcinoma, and secretory breast cancer) or for commonly diagnosed tumour types (e.g. lung cancer and colorectal cancer) known to be negative for other driver mutations.

15. How long does it take to get the patient sample returned from the Fast TRK lab?

Patient samples will be returned by the Fast TRK laboratory immediately after the testing is complete. Samples will be returned by overnight courier.

16. What if I have other questions?

Please review the requisition form for further information including details on shipping, sample preparation, patient eligibility criteria, technical specifications of the tests, etc. For any other inquiries, Health Care Practitioners are welcome to email fasttrk@bayer.com to be in touch with a representative from Bayer Medical Affairs.