Brief Report: Updated Efficacy and Safety Data From an Integrated Analysis of Entrectinib in Locally Advanced/Metastatic ROS1 Fusion-Positive Non–Small-Cell Lung Cancer

•Genetic alterations in ROS1 can lead to the expression of oncogenic fusion proteins in multiple tumor types, including in 1% to 2% of non–small-cell lung cancer (NSCLC) cases. Approximately 40% of patients with ROS1 fusion-positive NSCLC have baseline central nervous system (CNS) metastases, indicating the need for a treatment with CNS activity. Entrectinib, a potent ROS1 tyrosine kinase inhibitor with activity in the CNS, has previously demonstrated overall and intracranial efficacy, and a manageable safety profile, in patients with ROS1 fusion-positive NSCLC.•In this updated analysis with 4 additional patients and longer follow-up, the objective response rate (ORR) in the efficacy-evaluable population (N = 172) was 67%; median duration of response (DoR) was 20.4 months, and median progression-free survival was 16.8 months. In 51 patients with baseline CNS metastases, intracranial ORR was 49% and median intracranial DoR was 12.9 months. In a subgroup analysis in patients who had not received any prior systemic therapy in the metastatic setting, ORR was similar to that in the efficacy-evaluable population, but median DoR was numerically longer at 35.6 months. Most treatment-related adverse events were grade 1 to 2 and nonserious.•These data reinforce previous findings on the use of entrectinib for the treatment of patients with ROS1 fusion-positive NSCLC, and support current guidelines that recommend entrectinib as a first-line treatment option for these patients, including those with baseline CNS metastases. •Genetic alterations in ROS1 can lead to the expression of oncogenic fusion proteins in multiple tumor types, including in 1% to 2% of non–small-cell lung cancer (NSCLC) cases. Approximately 40% of patients with ROS1 fusion-positive NSCLC have baseline central nervous system (CNS) metastases, indicating the need for a treatment with CNS activity. Entrectinib, a potent ROS1 tyrosine kinase inhibitor with activity in the CNS, has previously demonstrated overall and intracranial efficacy, and a manageable safety profile, in patients with ROS1 fusion-positive NSCLC.•In this updated analysis with 4 additional patients and longer follow-up, the objective response rate (ORR) in the efficacy-evaluable population (N = 172) was 67%; median duration of response (DoR) was 20.4 months, and median progression-free survival was 16.8 months. In 51 patients with baseline CNS metastases, intracranial ORR was 49% and median intracranial DoR was 12.9 months. In a subgroup analysis in patients who had not received any prior systemic therapy in the metastatic setting, ORR was similar to that in the efficacy-evaluable population, but median DoR was numerically longer at 35.6 months. Most treatment-related adverse events were grade 1 to 2 and nonserious.•These data reinforce previous findings on the use of entrectinib for the treatment of patients with ROS1 fusion-positive NSCLC, and support current guidelines that recommend entrectinib as a first-line treatment option for these patients, including those with baseline CNS metastases.