1602 – Testing for neurotrophic tyrosine receptor kinase (NTRK) gene fusion status, in patients with locally advanced or metastatic solid tumours, to determine eligibility for larotrectinib

New MBS item.

This application requests new MBS items for NTRK (neurotrophic tyrosine receptor kinase) gene fusion testing, in patients with locally advanced or metastatic solid tumour to determine eligibility for larotrectinib. To identify NTRK-fusions, screening can be performed using immunohistochemistry (IHC) under MBS items 72846, 72847, 72849 and 72850. Positive IHC results must be followed with confirmatory testing, using a molecular method to verify the presence of a fusion (because over-expression of wildtype TRK (tyrosine receptor kinase) proteins may also be detected using IHC. Two appropriate methods are currently recommended to validate positive results: fluorescence in-situ hybridisation (FISH) and RNA-based next-generation sequencing (RNA-NGS). Screening for NTRK-fusions can routinely be performed using IHC under MBS items 72846, 72847, 72849 and 72850. New MBS items are sought for NTRK-fusion testing using FISH and RNA-NGS.

Type: Investigative

According to the applicant for 1602, "NTRK gene fusions have been reported across a wide range of solid tumour types as the primary oncogenic driver in both the adult and paediatric patient populations. Although considered a rare occurrence, overall incidence and prevalence of NTRK-fusions in the population are currently unknown. It has been reported that frequency of NTRK gene fusions varies by tumour localisation, from <1% to 3% in common tumour histologies (such as lung cancer and colorectal cancer) to approaching 100% in rare histologies (such as mammary analogue secretory carcinoma) and paediatric cancers (such as infantile fibrosarcoma). Current evidence suggests NTRK gene fusions are implicated in <1% of all solid tumours. NTRK-fusion cancer currently has no effective therapy to target the primary oncogenic driver leading to pathogenesis of this malignancy. As a result, overall survival for patients with advanced NTRK-fusion cancer is poor. Current standard of care for patients with unresectable or metastatic cancer includes cycling through multiple lines of untargeted, cytotoxic chemotherapy, where efficacy decreases. In addition, chemotherapy can be associated with significant toxicity, potentially causing secondary tumours and reduced quality of life. Thus, there is a high unmet need for an effective, well-tolerated, targeted therapy for adults and children with advanced NTRK gene fusion cancer."

• PASC meeting: 5 to 6 December 2019
• ESC meeting: 8 to 9 October 2020
• MSAC meeting: 26 to 27 November 2020