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....

As of July 20, 2022, 30 pts with a median age of 55.5 years (range 25–81) with TRK fusion lung cancer enrolled, including 12 pts with CNS metastases at baseline. The gene fusions involved NTRK1 (n = 24; 80%) or NTRK3 (n = 6; 20%)....In this larger dataset with longer follow-up, larotrectinib continued to demonstrate rapid and durable responses, extended survival, and favorable long-term safety in pts with advanced TRK fusion lung cancer, including those with CNS metastases.

Larotrectinib demonstrated rapid and durable responses, extended survival and a favourable long-term safety profile in patients with advanced lung cancer harbouring NTRK gene fusions, including in patients with CNS metastases. These results support testing for NTRK gene fusions in patients with lung cancer.

Pts with TRK fusion lung cancer enrolled in two larotrectinib clinical trials (NCT02576431 and NCT02122913) were included for this analysis....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, including in pts with CNS metastases.

ctDNA datawere available for 14 evaluable pts; 13 in which somatic alterations were detected. ctDNA analysis detected NTRK gene fusions in 46% of the pts at treatment start. Bythe data cut-off, 6 pts had a progression event with ctDNA data available for 5 pts. Potential acquired mutations were identified in 3 pts: one with NTRK1 F589L and G595R, one with SMAD4 R361C and the third with ARID1A K1238fs and FGFR2 R210Q mutations.

Patients with TRK fusion lung cancer enrolled in two larotrectinib clinical trials (NCT02576431 and NCT02122913) were included for this analysis. Larotrectinib was administered...The gene fusions involved were NTRK1 (n=21) and NTRK3 (n=5)….In this larger dataset with longer follow-up, larotrectinib demonstrated rapid and durable responses, extended survival, and a favorable long-term safety profile in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases.

20 patients with TRK fusion-positive lung cancer had been treated. The ORR by investigator assessment among 15 evaluable patients was 73% (95% CI, 45 to 92); one (7%) patient had a complete response, 10 (67%) had a partial response, three (20%) had stable disease, and one (7%) had progressive disease as best response. The median duration of response, progression-free survival, and overall survival were 33.9 months (95% CI, 5.6 to 33.9), 35.4 months (95% CI, 5.3 to 35.4), and 40.7 months (95% CI, 17.2 to not estimable), respectively....Larotrectinib is highly active with rapid and durable responses, extended survival benefit, and a favorable long-term safety profile in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. These findings support routine testing for NTRK fusions in patients with lung cancer.

Among 15 evaluable patients, ORR was 87% (95% confidence interval [CI] 60–98) 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%...Larotrectinib achieved rapid and durable responses with extended survival benefits and a favorable safety profile.

Pts with lung cancer harboring a NTRK gene fusion enrolled in two clinical trials (NCT02576431 and NCT02122913) were identified for this analysis. Larotrectinib 100 mg PO BID was administered...The gene fusions involved NTRK1 (n = 16; 80%) or NTRK3 (n = 4; 20%)....Among 15 evaluable pts, the confirmed ORR was 73% (95% CI 45–92): 1 complete response, 10 partial responses (PR), 3 stable disease (SD) and 1 progressive disease (PD)....

ORR was 71% (95% CI 42–92). ORR in pts with CNS metastases was 57% (95% CI 18–90). Median duration of response (DoR) was not estimable (NE; 95% CI 5.6–NE), with a 12-month DoR rate of 88%. Median PFS was also NE (95% CI 7.2–NE), with a 12-month PFS rate of 69%. Median overall survival (OS) was NE (95% CI 17.2–NE), with a 12-month OS rate of 91%....Larotrectinib demonstrated durable responses, extended survival and a favourable safety profile in pts with NTRK fusion lung cancer.

Eleven patients (79%) had fusions involving NTRK1 and three patients (21%) had fusions involving NTRK3...larotrectinib was shown to be highly active in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. The drug has a favorable safety profile.

116 adults (median age: 56 y, range 19–84 y; 53% female) with TRK fusion cancer were treated. Tumor types included thyroid cancer (22%), salivary gland cancer (19%), soft tissue sarcoma (16%), lung cancer (12%), colon cancer (7%), melanoma (5%), breast cancer (5%), GIST (3%), and 9 other types (≤2% each). NTRK fusions involved NTRK1 (43%), NTRK2 (3%), and NTRK3 (54%)....larotrectinib demonstrated robust and durable tumor-agnostic efficacy and favorable safety, supporting NTRK gene fusion testing in patients with solid tumors of any type.