Case-Based Overview: NTRK Fusion–Positive mCRC

Cathy Eng, MD, FACP, FASCO: The case that I was asked to present was a 68-year-old woman who presented with a 3-month history of intermittent abdominal pain and alternating constipation and diarrhea. She has a history of hypertension, hypercholesterolemia. This is well-managed. She's had a prior colonoscopy about 18 years ago at the age of 50, and that was unremarkable.

She denies tobacco use and has no known family history of cancer. On examination her abdomen was tender to deep palpation in the right lower quadrant. Her clinical work-up included blood work. Her hemoglobin was 11.9 g/dL, her hematocrit was 32%, her MCV [mean corpuscular volume] was 75 [fL] and her CEA [carcinoembryonic antigen] was 12.8 ng/mL.

Diagnostic studies revealed, following a CT [computed tomography] scan of the chest, abdomen and pelvis, that she had a 5-cm right-sided mass with multiple liver metastasis and some associated adenopathy around the colon.

A colonoscopy was completed on this patient, which revealed a tumor in the ascending colon. It was a non-obstructing tumor and biopsies were completed. The pathology report was consistent with a poorly differentiated adenocarcinoma. A biomarker score was sent off, including KRAS, NRAS, BRAF, MSI [microsatellite instability] status, as well as NTRK. She was determined to be, RAS wild type, BRAF wild type, MSIhigh, and NTRK positive.

Based upon these diagnostic studies, her staging appears to be consistent with a TXNXM1 tumor, her ECOG [Eastern Cooperative Oncology Group] performance status is 1.

My evaluation of this patient, here is an average-age patient with what appears to be newly diagnosed stage IV colorectal carcinoma. She has a non-obstructing tumor, so this does not indicate that she has to go to surgery. She has been determined to have an MSI-high tumor, which is obviously a good prognostic sign for this patient.

More importantly, she also has been found to have other molecular markers, which are also favorable in the sense that she is all RAS wild type. But she's also determined to be NTRK positive. This is the type of patient for whom we would proceed with systemic chemotherapy or systemic treatment versus proceeding with any type of surgical intervention.

The incidence of the NTRK fusion and colorectal carcinoma is extremely rare. It is probably less than 1% of all of our colorectal cancer patients. It's actually been evaluated based upon analysis completed by Caris Life Sciences, which noted that of 11,000 patients that they evaluated, it was present in about 0.23% of all patients. However, there appears to be increased incidence in MSI-high patients. In regard to the prognosis of these patients, much of the data are still very immature.

I would say, depending upon whether the patients had prior therapy, and taking into account whether they are MSI high or MSI stable, that also determines the overall prognosis. In this patient who is newly diagnosed, obviously they do have different options, but more importantly she is MSI high, which allows the opportunity for the role of immunotherapy as well.

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