As reported in the Journal of Clinical Oncology by Rafal Dziadziuszko, MD, and colleagues, an updated integrated analysis of three phase I or II trials of entrectinib in patients with advanced ROS1-positive non–small cell lung cancer (NSCLC) indicated that treatment continues to be associated with marked clinical benefit, including among patients with central nervous system (CNS) metastases.

The primary analysis of these trials supported the August 2019 approval of entrectinib for treatment of adults with ROS1-positive metastatic NSCLC.

Rafal Dziadziuszko, MD

Study Details

The analysis included an efficacy-evaluable population of 161 patients with locally advanced or metastatic NSCLC in the phase I or II ALKA-372-001, STARTRK-1, and STARTRK-2 trials who received oral entrectinib at ≥ 600 mg once daily until disease progression or unacceptable toxicity and had follow-up of 6 months or longer. Prior lines of systemic treatment were zero in 37% of patents, one in 40%, and two or more in 23%. A total of 46 patients had CNS metastases at baseline on blinded independent central review, with 24 having measureable disease.

Key Findings

The median duration of follow-up was 15.8 months (interquartile range [IQR] = 10.4–22.9 months). The median duration of treatment was 10.7 months (IQR = 6.4–17.7 months).

Objective response on blinded independent central review was observed in 108 patients (67.1%, 95% confidence interval [CI] = 59.3%­–74.3%), including complete response in 14 (8.7%); an additional 14 patients (8.7%) patients had stable disease. Median duration of response was 15.7 months (95% CI = 13.9–28.6 months), with 63% of responses maintained at 12 months.  

Median progression-free survival was 15.7 months (95% CI = 11.0–21.1 months), with a 12-month rate of 55%. Median overall survival was not reached (95% CI = 28.3 months–not estimable), with a 12-month rate of 81%.

Among the 46 patients with blinded independent central review–assessed CNS metastases at baseline, intracranial response was observed in 24 (52.2%, 95% CI = 37.0%–67.1%), including complete response in 8 (17.4%). Median intracranial progression-free survival was 8.3 months (95% CI = 6.4–15.7 months), with a 12-month rate of 44%. Responses were maintained at 12 months in 55.0% of responders.

Among 24 patients with blinded independent central review–assessed measurable CNS metastases, intracranial response was observed in 19 (79.2%, 95% CI = 57.9%–92.9%), including complete response in 3 (12.5%). Median intracranial progression-free survival was 12.0 months (95% CI = 6.2–19.3 months). Median duration of intracranial response was 12.9 months, with responses maintained at 12 months in 55.0% of responders.

The safety profile in the updated analysis was similar to that in the primary analysis, with no new safety signals being identified.

The investigators concluded, “Entrectinib continued to demonstrate a high level of clinical benefit for patients with ROS1 fusion–positive NSCLC, including patients with CNS metastases.”

Fabrice Barlesi, MD, PhD, of Gustave Roussy Cancer Campus, Medical Oncology, Villejuif, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by F. Hoffmann-La Roche Ltd. For full disclosures of the study authors, visit ascopubs.org.