How I treat NTRK gene fusion-positive cancers

Abstract

NTRK fusions are found at low frequencies (commonly <1%) in a range of common tumour types and at high frequencies (up to or greater than 90%) in rare cancer types (secretory breast carcinoma, mammary analogue secretory carcinoma and infantile fibrosarcoma). The fusions typically occur in a mutually exclusive fashion with other strong mitogenic drivers, and it is of significant importance to identify patients in order to offer transformative treatment with TRK inhibitors. Larotractinib or entrectinib have resulted in fast and durable response with few and reversible adverse events. Even though on-target resistance may occur, second generation TRK inhibitors are in development and have shown promising activity. Diagnostic strategies must be applied, considering available assays and specific tumour types.

Keywords: NTRK fusion; TRK inhibitors.

Figure 1

NTRK fusion detection: the ESMO proposal. FISH, fluorescence in situ hybridisation; IHC, immunohistochemistry; NGS, next-generationsequencing; NTRK, neurotrophic tropomyosin receptor kinase; RT-PCR, reverse-transcriptasePCR