entrectinib (Rozlytrek®) is accepted for use within NHSScotland...Indication under review: as monotherapy for the treatment of adult patients with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.

Rozlytrek can also be used for treating adults with advanced non-small-cell lung cancer that has a genetic abnormality called ROS1 gene fusion. It should be used only if the patient has not been treated previously with a medicine that blocks ROS1.

...Harbouring an NTRK fusion or ROS1 activating gene alteration identified using CGP...

...Confirmed diagnosis of a ROS1 gene fusion-positive malignancy, other than NSCLC, that has been identified using an analytically validated sequencing technique....

In total, 20 pts with ROS1-fp NSCLC and 10 pts with NTRK-fp solid tumours (5 salivary, 1 breast, 1 colorectal, 1 NSCLC, 1 sarcoma, 1 thyroid) were efficacy evaluable. For both cohorts, median survival follow-up was 38.6 mos and ORR was 70%....The 24-mos OS rates were 65% (ROS1-fp NSCLC) and 90% (NTRK-fp solid tumours). In pts without baseline CNS mets by investigator, ORR was 76% (ROS1-fp NSCLC; n=13/17) and 75% (NTRK-fp solid tumours; n=6/8). In pts with baseline CNS mets by BICR (3 ROS1-fp; 1 NTRK-fp), one pt (NTRK-fp) had an IC response....Entrectinib showed deep and durable responses and manageable safety in Japanese pts with locally advanced/metastatic ROS1-fp NSCLC or NTRK-fp solid tumours

This updated analysis with longer follow-up provides further evidence that entrectinib is associated with deep and durable responses in Chinese pts with NTRK-fp solid tumours or ROS1-fp NSCLC.

In patients with BICR-assessed baseline CNS metastases (n=51), median IC-ORR was 49% (25/51; 95% CI 34.8-63.4); median IC-DoR was 12.9 months (95% CI 7.6-22.5); median IC-PFS was 12.0 months (95% CI 6.7-15.6). In patients who received entrectinib as first-line treatment (n=67; exploratory analyses; Table), ORR was 69% (95% CI 56.2-79.4), median DoR was 35.6 months (95% CI 13.9-38.8); median PFS was 17.7 months (95% CI 11.8-39.4). In this updated analysis with longer follow-up and a larger patient population, entrectinib continues to demonstrate overall and intracranial efficacy, and a manageable safety profile in patients with ROS1-fp NSCLC.

Adult Chinese pts with ROS1- and TRK- TKI-naïve, ROS1-fp locally advanced/metastatic NSCLC or NTRK-fp solid tumours were enrolled....In Chinese pts with locally advanced/metastatic ROS1-fp NSCLC or NTRK fp solid tumours, with or without baseline CNS metastases, entrectinib induced deep and durable responses.

SA-PRO populations comprised patients with NTRK fusion-positive solid tumours (N = 88) or ROS1 fusion-positive non-small-cell lung cancer (N = 180) who received one or more doses of entrectinib...Both cohorts reported low-to-moderate symptom burden at baseline, which was maintained or trended towards clinically meaningful improvement.

In patients with ROS1-positive NSCLC, the ORR was 67.1% (95% CI 59.25% to 74.27%) and the median DOR was 15.7 months (95% CI 13.9-28.6 months)....ROS1-rearranged NSCLC indication, entrectinib showed antitumour activity by inducing a relevant ORR of some durability, confirmed with longer follow-up and a larger dataset.

We report the results of an updated integrated analysis of three phase I or II clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) of the ROS1 tyrosine kinase inhibitor, entrectinib, in ROS1 fusion-positive NSCLC….The ORR was 67.1% (n = 108, 95% CI, 59.3 to 74.3)...The 12-month PFS rate was 55% (median PFS 15.7 months), and the 12-month OS rate was 81%...Entrectinib continued to demonstrate a high level of clinical benefit for patients with ROS1 fusion-positive NSCLC, including patients with CNS metastases.

Entrectinib induced clinically meaningful intracranial responses in pts with NTRK-fp or ROS1-fp NSCLC with CNS metastases at baseline. Intracranial ORR, median intracranial DoR and median intracranial PFS for these two cohorts are shown in the table.

This updated analysis, using a larger dataset with longer follow-up, shows that entrectinib induces clinically meaningful responses in pts with ROS1-fp NSCLC, including pts with CNS metastases at baseline…

In the 25 patients with measurable baseline CNS metastases, the intracranial ORR was 80% (95% CI: 59.3–93.2), median intracranial DoR was 12.9 months, and median intracranial PFS was 8.8 months. Among 18 patients with CNS-only progression on previous crizotinib treatment, two achieved a partial response (11%) and four had stable disease (22%). In seven patients with measurable CNS disease from this cohort, the intracranial ORR was 14% (1 partial response)....Entrectinib is active and achieves prolonged survival in ROS1 TKI–naïve patients with ROS1 fusion–positive NSCLC.