Testing for NTRK Fusion–Positive Metastatic Colon Cancer

Cathy Eng, MD, FACP, FASCO: The preferred methods for testing for the NTRK fusion, I think most of us nowadays are utilizing next-generation sequencing [NGS]. I think that's commonly being done across all, not only academic institutions, but community practices as well. I think it is more important that you also learn more about the companies that you're working with, where you're sending out the specimens, in regard to your NGS panels.

There will be some that may miss the NTRK fusion. The majority of NGS panels nowadays, or the evaluation for the specimens, includes the use of RNA sequencing, which will then have increased sensitivity and specificity.

In regard to testing for the platforms that you're looking at with the NTRK fusion, once again, you really need to evaluate where you're sending out your specimens. You need to ensure that they are actually able to evaluate NTRK fusion appropriately.

The majority of companies that are looking for these NTRK fusions are able to capture and track 1, 2, and 3, which are the forms that we were looking for. But more importantly, once again it's extremely significant to make sure that all patients are tested for microsatellite instability [MSI].

That is recommended in all patients regardless of whether you're considering an NTRK inhibitor. As everybody knows, there is a significant role for immunotherapy in our patient population that has been determined to be MSI high. And then obviously, more importantly for the younger patients, those patients should be evaluated by a genetics group.

Transcript edited for clarity.

Case: A 68-Year-Old Woman With Metastatic NTRK Fusion-Positive Colon Cancer

Initial presentation

• A 68-year-old woman presented with a 3-month history of intermittent abdominal pain, and alternating constipation/diarrhea
• PMH/SH: hypertension and hypercholesterolemia, medically managed; colonoscopy at age 50 was unremarkable; never smoker; no family history of cancer
• PE: abdomen tender on deep palpation in the right lower quadrant

Clinical workup

• Labs: Hb 11.9, Hct 32%, MCV 75 fL, CEA 12.8 ng/mL
• Chest/abdominal/pelvic CT showed a 5-cm right sided bowl mass and multiple hepatic lesions, and regional lymphadenopathy
• Colonoscopy revealed a 5-cm mass in the ascending colon, biopsy was taken
• Pathology: grade 3 poorly differentiated adenocarcinoma, with invasion of the submucosa
• Biomarkers: KRAS-wt, NRAS-wt, BRAF-, NTRK+; MSI-H
• Stage TXNXM1; ECOG PS 1