…the NCCN Panel voted that larotrectinib and entrectinib are both preferred (category 2A) as first-line therapy for patients with NTRK gene fusion-positive metastatic disease.

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.

...- Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories....

...we estimate and compare long term benefit for pts receiving larotrectinib or entrectinib for NTRK gene fusion-positive non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) by extrapolating survival curves to generate expected life-years (LYs) and quality-adjusted life-years (QALYs)....In the larotrectinib trials, response rates were 86% and 33% in NSCLC and CRC, respectively....Larotrectinib improved survival and quality adjusted survival vs entrectinib.

Pts treated with larotrectinib in 2 clinical trials were analysed. NTRK gene fusions were determined by local testing before enrolment. Larotrectinib was administered at 100 mg twice daily….ORR was 83% (95% confidence interval [CI] 61–95; 2 complete response, 17 partial response, 4 stable disease). Median duration of response (DoR) was not reached (95% CI 9.5–not estimable [NE]), with a 12-month DoR rate of 72%. Median progression-free survival was not reached (95% CI 9.9–NE). Median overall survival was 40.7 months (95% CI 19.4–NE)....Larotrectinib demonstrated durable responses, extended survival benefit, and a favourable safety profile in patients with advanced lung cancer harbouring NTRK gene fusions, including those with treatment-naive NSCLC or with prior EGFR inhibitor therapy.

The gene fusions involved NTRK1 (n =21; 81%) or NTRK3 (n =5; 19%)...In this larger dataset, larotrectinib demonstrated rapid and durable responses, extended survival, and a favorable long-term safety profile in pts with advanced lung cancer harboring NTRK gene fusions...

Among 15 evaluable patients, ORR was 87%...as per IRC...and 73% (95% CI 45–92) per INV. In patients with baseline CNS metastases, ORR was 88% (95% CI 47–100) per IRC and 63% (95% CI 25–91) per INV….Larotrectinib achieved rapid and durable responses with extended survival benefits and a favorable safety profile. These data support testing for NTRK gene fusions in patients with lung cancer.

Patients with lung cancer harbouring an NTRK gene fusion enrolled in two clinical trials were pooled for this analysis. Larotrectinib 100 mg BID was administered...Eleven patients had fusions involving NTRK1 and three patients had fusions involving NTRK3...The ORR with larotrectinib was 71% (95% CI 42–92%): one patient had a complete response, nine had partial responses, three had stable disease and one had progressive disease.

As of July 15, 2019, 14 patients with metastatic TRK fusion lung cancer were enrolled: 13 with non-small cell lung cancer and 1 with small cell lung cancer. The ORR with larotrectinib was 71% (95% CI 42–92%): 1 patient had a complete response, 9 had partial responses, 3 had stable disease and 1 had progressive disease. The ORR in patients with CNS metastases was 57% (95% CI 18–90%). The overall DoR ranged from 1.9+ to 28.7+ months…In this updated analysis, larotrectinib was shown to be highly active in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases.