NTRK-Targeted Therapy in Colon Cancer: Dosing and Management

Cathy Eng, MD, FACP, FASCO: In regard to the dosing for larotrectinib, the standard dosing is 100 mg bid [twice a day]. Once again, it comes in an oral and a liquid form. And obviously that’s advantageous for some of our patients, not necessarily just colorectal cancer patients, keeping in mind that NTRK is basically tumor agnostic.

There were some grade 3 toxicities, but no grade 4 or 5 toxicities.

Of the toxicity seen with larotrectinib, for grade 3 toxicities, they were fairly mild, one being anemia. That was in about 14% of patients. I would say for any oral agent, obviously you have to be very mindful of how well the patient is adhering with taking the medications as directed.

You still have to follow the patients regardless of the fact that it is more convenient for them to take an oral agent. My tendency for any oral agent is to follow the patients at least every 2 weeks for the first month. Then, give or take, maybe considering that as well for the second month. And then after that, I may cut it back to just once a month. That is my tendency with all patients on oral agents, not just the NTRK inhibitors.

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