NTRK Fusion–Positive Colon Cancer: Final Thoughts


Cathy Eng, MD, FACP, FASCO: There is a drug specific to NTRK fusion resistance to larotrectinib and also specifically for the NTRK inhibitors, and that is NTRK1 G595R. There is a drug specific to that called LOXO-195, which is approved to be utilized in that setting.

I would say that basically this literature regarding the NTRK fusion and its significance is important across all malignancies. Although I focus specifically on colorectal carcinoma, the NTRK fusion is more common in other malignancies, such as papillary thyroid carcinoma, salivary gland carcinoma, and more common in pediatric tumors.

It is advantageous for other malignancies, not necessarily colorectal carcinoma, but it appears to have a role, specifically even higher in the MSI [microsatellite instability]-high positive colorectal cancer tumors. And the fact that it's an oral agent with such significant response.

Once again, if the patient tolerates it well and given that there are several patients who we treat, on a day-to-day basis, with refractory colorectal carcinoma that are surgically unresectable, if they're NTRK positive, obviously this is another drug that would be advantageous in the armamentarium to treat our metastatic colorectal cancer patients.

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
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