Breast cancer: Invasive Breast Cancer...ADDITIONAL TARGETED THERAPIES AND ASSOCIATED BIOMARKER TESTING FOR RECURRENT OR STAGE IV (m1) DISEASE…Any…NTRK fusion…entrectinib

ROZLYTREK is a kinase inhibitor indicated for the treatment of...Adult and pediatric patients older than 1 month of age with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, as detected by an FDA-approved test without a known acquired resistance mutation.

Pts with locally advanced/metastatic NTRK-fp breast cancer with or without CNS metastases were enrolled....Median DoR was 12.9 months (95% CI 4.2–not evaluable [NE]), median PFS was 10.1 months (95% CI 5.1–NE) and median OS was 19.2 months (95% CI 5.1–NE)....In this updated analysis with longer follow-up, entrectinib continues to show deep and durable responses in pts with NTRK-fp breast cancer and was well tolerated.

Entrectinib was evaluated in 3 global phase 1/2 clinical trials (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]), where it demonstrated strong and durable systemic and intracranial efficacy in pts with NTRK-fp solid tumors, including those with breast cancer. In this updated integrated analysis, entrectinib induced objective responses in all pts with NTRK-fp breast cancer who had data available, and was generally well tolerated with no discontinuations due to TRAEs.

The efficacy-evaluable population comprised 54 adults with advanced/metastatic NTRK fusion-positive tumours...In the integrated analysis population, responses to entrectinib occurred in all tumour types and included 4 CRs (7.4%)....entrectinib was well tolerated and induced clinically meaningful, durable responses in NTRK fusion-positive BC.

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.