The oral TRK inhibitor larotrectinib (Vitrakvi) is now listed on the PBS for the treatment of some NTRK gene fusion positive tumours in children and adults.
From 1 July, larotrectinib will be subsidised for the treatment of children aged from one month diagnosed with NTRK gene fusion positive tumours, and for adults with NTRK fusion positive advanced mammary analogue secretory carcinoma (MASC, a form of salivary gland cancer) and secretory breast cancer.
NTRK fusion genetic testing (NGS or FISH) to identify patients eligible for larotrectinib will be funded by a newly created MBS item.
The listings were welcomed by Associate Professor Jordan Hansford, a paediatric oncologist at the Women’s and Children’s Health Network, Adelaide, and researcher at the South Australian Health and Medical Research Institute (SAHMRI).
He said studies involving patients with in NTRK gene fusion positive tumours had shown a high rate and durability of responses delivered by larotrectinib.
“Being able to precisely treat the oncogenic driver is a major step forward – especially in the context of childhood cancers, aggressive cancers and cancers for which there are limited treatment options,” he said.
“The message is clear – test for NTRK gene fusions as part of broad molecular testing. Next generation sequencing allows for efficient multiplex testing with the ability to detect NTRK gene fusions as well as other key oncogenic drivers.”
Professor Hansford said solid tumours harbouring an NTRK gene fusion could occur anywhere in the body with varying frequency and were a heterogeneous group, ranging from the ultra-rare infantile fibrosarcoma and hard-to-treat gliomas to some of Australia’s most common cancers such as melanoma and bowel cancer.
He noted that NTRK fusion was most common in childhood cancers as well as salivary gland and secretary breast cancer – the tumour types for which the medicine will be reimbursed.
“These cancers have not traditionally been considered as one group and have typically had different treatment protocols based on the tumour site of origin,” he said.
In trials of patients with NTRK fusion cancer, larotrectinib has shown pan-tumour efficacy, with clinical benefit across more than 15 unique tumour types.
“Access to a generally well tolerated and effective targeted treatment, able to elicit durable responses in patients with NTRK gene fusions regardless of the site of the tumour, is very much welcome news,” concluded Professor Hansford
Until now, there has been no PBS-listed therapy specifically for patients with NTRK fusion cancer. The listing of larotrectinib was recommended by the PBAC in 2021, when it acknowledged there was “a clinical need for effective therapies for patients with rare cancers harbouring NTRK fusions, for which there are few effective standard of care treatments.”
In its decision summary the PBAC noted that the Medical Oncology Group of Australia (MOGA) had expressed its strong support for the larotrectinib submission for PBS listing, categorising it as one of the therapies of “highest priority for PBS listing” on the basis of pooled analysis of the single-arm LOXO-001, NAVIGATE, and SCOUT trials.
However at its November 2021 meeting, the PBAC deferred making its decision on whether to recommend the PBS listing of larotrectinib for the treatment of patients with NTRK fusion tumours that are either unresectable locally advanced, metastatic, or locally advanced and would otherwise require disfiguring surgery or limb amputation to achieve a complete surgical resection.