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.