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Crizotinib (Xalkori) has approval as first-line therapy for ROS1 fusion-positive metastatic NSCLC but has poor CNS penetration, the authors noted, adding that in about half of patients treated with crizotinib, initial progression occurs only in the CNS. Entrectinib is designed to cross the blood-brain barrier, and preclinical studies showed that the agent achieves high CNS concentrations, which were associated with strong efficacy in brain-tumor models. Integrated Analysis For the analysis, the investigators evaluated entrectinib in three phase I or II clinical trials of patients with locally advanced or metastatic ROS1 fusion-positive NSCLC. A preliminary analysis of a 53-patient efficacy-evaluable population showed a 77% objective response rate (ORR) and a median duration of response (DoR) of 24.6 months.

New yorkUnited statesMemorial sloan kettering cancer centerFabrice barlesiAnna faragoAlexander drilonCharles bankheadCrizotinib xalkoriHospital cancer centerGustave roussy cancer campusNew york cityMassachusetts general hospital cancer centerMedpage todayNon small cell lung cancerSecondary malignant neoplastic diseaseLung cancer