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Earlier Use of Larotrectinib in Mismatch Repair–Deficient TRK Fusion–Positive Metastatic Colon Cancer

By: Joseph Fanelli
Posted: Tuesday, September 27, 2022

A case study presented in the journal Cureus highlighted a patient with a deficiency in mismatch repair/microsatellite instability–high (MSI-H) metastatic colon cancer harboring an NTRK fusion who had a “marked and durable” response to treatment with larotrectinib after disease progression on immunotherapy. Pashtoon M. Kasi, MD, of the Weill Medical College at Cornell University, New York, and colleagues noted that the patient’s response to larotrectinib may indicate the drug’s potential as an option in earlier treatment lines.

“This case illustrates the value of serial ctDNA [circulating tumor DNA] ([next-generation sequencing] and tumor-informed)-based testing with ctDNA kinetics and [measurable residual disease] testing as predictive markers of response to systemic therapy,” the authors concluded.

The authors described the case of a 43-year-old woman who, after initially being diagnosed with stage IIB colon cancer and deferring adjuvant chemotherapy, experienced recurrent metastatic colon cancer with metastases to the peritoneum. A ctDNA-based liquid biopsy subsequently revealed MSI-H status, which was also confirmed by tissue testing.

After experiencing disease progression after four cycles of treatment with pembrolizumab, the patient received the TRK inhibitor larotrectinib to specifically target cancers harboring NTRK fusions. After 5 weeks of treatment, CT scans revealed a decrease in the size of the patient’s largest peritoneal metastasis in the right lower quadrant. In addition, the patient clinically improved within 1 week of starting treatment, with decreased pain and weight gain, the authors wrote.

After 4 months of treatment with larotrectinib, the patient underwent curative-intent surgical resection of the tumor mass. A complete cytoreduction was achieved, and hyperthermic intraperitoneal chemotherapy was deferred. About 26 months after treatment, the patient had no evidence of disease recurrence.

“After surgery, the patient has been fully functional and back to work, with excellent performance status and quality of life,” the authors said.

Disclosure: For full disclosures of the study authors, visit ncbi.com.


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