Biomarker NTRK Coverage from Every Angle
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How Common Are NTRK1/2/3 Fusions in Colorectal Cancer?

By: Kayci Reyer
Posted: Friday, October 22, 2021

According to research presented virtually during the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract 444P), NTRK1/2/3 fusions may appear infrequently among patients with metastatic colorectal cancer harboring mismatch repair deficiency and/or microsatellite instability. Magali Svrcek, MD, PhD, of Hopital Saint-Antoine in Paris, and colleagues also determined that pan-TRK immunohistochemistry does not appear to be a reliable prognostic tool in this patient population.

“Optimal testing algorithms for theranostic [purposes] remain to be defined in this setting,” concluded the authors.

The study included tumor samples from 172 patients; 38 samples were paired to include both primary and metastasis specimens, and 134 were from primary tumors alone. Fluorescent in situ hybridization analysis identified NTRK fusion genes in 10 patients (NTRK1 = 8; NTRK3 = 2), 5 of whom were pan-TRK–positive. Of those patients, six, including four who were pan-TRK–positive, were found via Archer assay to harbor TPM3-NTRK1 (n = 2), LMNA-NTRK1 (n = 2), ETV6-NTRK3 (n = 1), and EML4-NTRK3 (n = 1) fusion transcripts.

Though most of the cases harboring fusions were sporadic (n = 8), two were associated with Lynch syndrome or germline mismatch repair mutations, with either MSH2/MSH6 loss or isolated MSH6 expression loss. A KRAS mutation and a BRAF V600E mutation were identified in a Lynch syndrome–related tumor and a sporadic tumor, respectively. Immune checkpoint inhibitor therapy was administered to four patients with NTRK-positive tumors. Of those patients, two achieved a complete response, one achieved a partial response, and one experienced primary resistance.

Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.



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