Clinical benefit with entrectinib was confirmed among patients with ROS1 fusion-positive non-small cell lung cancer (NSCLC), including those with baseline central nervous system (CNS) metastases, according to an updated integrated analysis of phase 1 and 2 trials published in the Journal of Clinical Oncology.

This integrated analysis expands a prior analysis with additional patients and longer follow-up. The study included 161 patients with ROS1 fusion-positive, locally advanced or metastatic NSCLC from the phase 1 or 2 ALKA-372-001, STARTRK-1 ( Identifier: NCT02097810), and STARTRK-2 ( Identifier: NCT02568267) trials who were treated with entrectinib. The co-primary endpoints were objective response rate (ORR) and duration of response. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

The ORR was 67.1%, which included complete responses among 8.7% of patients. The highest responses occurred among patients whose disease harbored a ROS1 fusion with CD74 at 72.9%, whereas the lowest response occurred in patients with the SLC34A2 fusion partner at 57.1%.

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The ORR remained high for patients with CNS metastases at baseline at 62.5% compared with 69.5% among patients without CNS disease at baseline. Intracranial ORR was 79.2% among patients with baseline CNS disease, which included 3 patients who experienced an intracranial complete response.

The median duration of response was 15.7 months.

During a median follow-up of 15.8 months, the median PFS was 15.7 months, which translated to a 12-month rate of 55%. The OS data are immature with a median not yet reached and a 12-month rate of 81%. 

The majority of treatment-related adverse events (TRAEs) were grade 1 to 2, with the most common grade 3 TRAEs including weight increase, alanine aminotransferase elevation, and diarrhea. Grade 4 TRAEs developed among 7 patients, and there were no grade 5 events reported. TRAEs led to a dose reduction or interruption among 29.0% and 30.5% of patients, respectively, and discontinuation among 4.3% of patients.

The authors concluded that this analysis showed that “entrectinib continued to demonstrate a high level of clinical benefit for patients with ROS1 fusion-positive NSCLC, including those with CNS metastases at baseline.”


Dziadziuszko R, Krebs MG, De Braud F, et al. Updated integrated analysis of the efficacy and safety of entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small-cell lung cancer. J Clin Oncol. Published online March 1, 2021. doi:10.1200/JCO.20.03025