Doebele RC, Drilon A, Paz-Ares L, et al. - The anti-tumor activity of entrectinib (a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C) against NTRK gene fusion-positive solid tumors has been demonstrated including its CNS activity as it can penetrate the blood-brain barrier. Researchers sought to illustrate an integrated effectiveness and safety analysis of patients with metastatic or locally advanced solid tumors harboring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials. The pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) comprised the integrated database. In these trials, patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumors were included and were provided entrectinib orally at a dose of at least 600 mg once per day in a capsule. In ALKA-372–001, enrollment of patients was done from Oct 26, 2012, to March 27, 2018; in STARTRK-1, from Aug 7, 2014, to May 10, 2018; and in STARTRK-2, from Nov 19, 2015 (enrolment is ongoing). On May 31, 2018 (the data cutoff date for this analysis), 54 adults with advanced or metastatic NTRK fusion-positive solid tumors were the efficacy-evaluable population comprising ten different tumor types and 19 different histologies. Outcomes revealed durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumors in correlation to receipt of entrectinib; the patients well-tolerated entrectinib with a manageable safety profile. In view of these results, they suggest entrectinib as a safe and active treatment option for patients with NTRK fusion-positive solid tumors and recommend testing for NTRK fusions routinely to increase the therapeutic options available for patients with NTRK fusion-positive solid tumors.