Soft Tissue Sarcoma: Useful in certain circumstances…Larotrectinib (for NTRK gene-fusion sarcomas).

We’re delighted to announce that a new drug, larotrectinib, has been approved for the treatment of certain sarcomas in England. ‘Sarcoma UK welcomes today’s approval of larotrectinib. Made available for use by the Cancer Drugs Fund and approved by NICE (National Institute for Health and Care Excellence) larotrectinib is a new type of ‘histologically-independent’ drug that targets tumours based on their genetic makeup. It works by targeting the specific NTKR genetic abnormality in tumours meaning patients are treated according to the genetics of their tumour rather than where it is in the body.

Tumor types included thyroid cancer (22%), salivary gland cancer (19%), soft tissue sarcoma (16%)...TRK fusions involved NTRK1 (43%), NTRK2 (3%), and NTRK3 (54%)….In an expanded data set of adults with TRK fusion cancer, larotrectinib demonstrated robust and durable tumor-agnostic efficacy and favorable safety, supporting TRK testing in patients with solid tumors of any type.

The ORR with larotrectinib in adult and pediatric patients with sarcoma harboring an NTRK fusion was 74% (95% CI 52–90) and 94% (95% CI 82–99), respectively. Objective responses were observed in patients with soft tissue sarcomas, GISTs, and infantile fibrosarcoma.

18 (47%) had infantile fibrosarcoma, 15 (39%) other soft tissue sarcoma, 2 (5%) thyroid cancer and 1 (3%) each had gastrointestinal stromal tumor, melanoma, or mesoblastic nephroma.…In 34 evaluable pts, the overall response rate was 94%: 12 CRs, 18 confirmed PRs, and 2 PRs pending confirmation; 2 had stable disease....Larotrectinib treatment resulted in a high and durable response rate in pediatric pts with TRK fusion cancer...

...adult subset of pts with TRK fusion cancer treated with larotrectinib. Cancer types included salivary gland (23%) and thyroid cancer (19%), soft tissue sarcoma (14%), lung cancer (13%), colon cancer and melanoma (7% each), GIST (5%), and bone sarcoma, cholangiocarcinoma, and appendiceal, breast, and pancreas cancer (≤2% each). In 74 pts evaluable per INV, the ORR was 76% with 9% CR, 57% confirmed PR, 9% PR pending confirmation, 12% SD, 11% PD, and 1% not determined...In 65 pts evaluable per IRC, the ORR was 68% with 17% CR, 51% PR, 15% SD, 12% PD, and 5% NE....Larotrectinib demonstrated robust tumor-agnostic efficacy and a favorable safety profile in adult pts with TRK fusion cancer.

Among enrolled patients harbouring TRK fusion-positive cancers, eight (47%) had infantile fibrosarcoma, seven (41%) had other soft tissue sarcomas, and two (12%) had papillary thyroid cancer….14 (93%) of 15 patients with TRK fusion-positive cancers achieved an objective response as per Response Evaluation Criteria In Solid Tumors version 1.1...The TRK inhibitor larotrectinib was well tolerated in paediatric patients and showed encouraging antitumour activity in all patients with TRK fusion-positive tumours.