Updated Data Support Significant Clinical Benefit of Entrectinib in ROS1 Fusion+ NSCLC

Data from the Journal of Clinical Oncology found that entrectinib resulted in high-level clinical benefit for patients with ROS1 fusion–positive non–small cell lung cancer, regardless of CNS metastases status.

Using entrectinib (Rozlytrek) to treat patients with locally advanced or metastatic ROS1 fusion–positive non–small cell lung cancer (NSCLC) shows a significant clinical benefit, according to data from an updated analysis of 3 clinical trials published in the Journal of Clinical Oncology.1

The high-level clinical benefit was also sustained for patients with CNS metastases when treated with entrectinib.

“In this updated analysis, comprising more patients and a longer follow-up than the primary analysis, entrectinib continued to demonstrate a high level of clinical benefit for patients with ROS1 fusion–positive NSCLC, including those with CNS metastases at baseline,” wrote the investigators.

A total of 161 patients with NSCLC harboring a ROS1 fusion who received 600 mg or more of entrectinib orally once daily were evaluated at a follow-up of 6 months or more, with a median treatment duration of 10.7 months (IQR, 6.4-17.7).

An analysis of 108 patients found an overall response rate (ORR) of 67.1% (95% CI, 59.3%-74.3%). The 12-month duration of response rate was 63%, with a median duration of response of 15.7 months.

The 12-month progression-free survival (PFS) rate was recorded at 55%, with a median PFS of 15.7 months. While the median overall survival (OS) rate was not estimable, the 12-month OS rate was 81%.

When focusing on the 24 patients who had measurable baseline CNS metastases, the research found an intracranial ORR of 79.2% (95% CI, 57.9%-92.9%), with a median intracranial PFS of 12.0 months (95% CI, 6.2-19.3). The median intracranial duration of response for this cohort was 12.9 months, with a 12-month rate of 55%.

No new safety signals were reported in this updated analysis when compared with the safety profile of the primary analysis.

“This updated integrated analysis represents the largest prospective trial in patients with locally advanced or metastatic ROS1 fusion–positive NSCLC and supports the strong activity of entrectinib, both overall and within the CNS,” wrote the investigators.

The co-primary end points of the data were blinded independent central review–assessed ORR and duration of response. Secondary end points included PFS, OS, intracranial ORR, intracranial duration of response, intracranial PFS, and safety.

The research was limited by the single-arm design and small sample size, as only 108 patients were evaluated on entrectinib. More, no mandatory requirement for post-progression tissue collection existed in this research, and the acquired resistance profile for entrectinib has not yet been fleshed out.

“As well as confirming the overall efficacy of entrectinib, our results provide strong evidence that entrectinib can treat existing CNS metastases and may have a potential CNS-protective effect in patients without CNS involvement at baseline,” wrote the investigators. “These data will help physicians to make more informed treatment decisions for their patients.”

The trials examined also served as the rationale for the approval of entrectinib in 2018 for adults and pediatric patients 12 years of age and older with NTRK gene fusion–positive solid tumors that do not have a known acquired resistance mutation, are metastatic or unlikely to benefit from surgical resection, and have progressed on treatment or have no satisfactory standard therapy.2


1. 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 March 1, 2021. doi:10.1200/JCO.20.03025

2. FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC. FDA. August 15, 2019. Accessed April 2, 2021. https://bit.ly/39BVXog