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.

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

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

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 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

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.

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…

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.

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.