preheader BJMO

Entrectinib confirms its overall and intracranial efficacy in patients with ROS1-fusion positive metastatic NSCLC

The identification of actionable biomarkers like ROS1 has brought about significant progress in the treatment of non-small cell lung cancer (NSCLC). An integrated analysis of the pivotal phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials previously demonstrated a high objective response rate among the patients with ROS1-fusion positive metastatic NSCLC who were treated with entrectinib. An updated analysis with longer follow-up and a larger patient population now confirmed the efficacy of entrectinib.

ROS1 gene rearrangements can lead to constitutively active fusion proteins that are targetable oncogenic drivers in non-small cell lung cancer (NSCLC). Entrectinib, a potent ROS1 tyrosine kinase inhibitor (TKI), has demonstrated efficacy and central nervous system (CNS) activity in patients with ROS1-fusion positive metastatic NSCLC from the integrated analysis of the phase I/II studies STARTRK-1 (NCT02097810), STARTRK‑2 (NCT02568267) and ALKA-372-001 (EudraCT 2012-000148-8). After a median follow-up of 15.8 months, the objective response rate (ORR) was 67% (N=108/161). At IASLC WCLC 2022, updated data from this ongoing analysis were presented.

Study design

Adults with locally advanced/metastatic ROS1-fusion positive NSCLC who received at least one dose of entrectinib and had ≥12 months of follow-up from first post-treatment initiation tumour assessment, were included in the efficacy analysis. The safety-evaluable population comprised all patients who received at least one dose of entrectinib. Tumour assessments (by blinded independent central review [BICR] per RECIST v1.1) were performed at the end of cycle 1 (Week 4) and then every 8 weeks. Primary endpoints are objective response rate (ORR) and duration of response (DoR). Secondary endpoints included progression‑free survival (PFS), overall survival (OS), intracranial (IC)‑ORR, IC‑DoR, IC-PFS and safety. Efficacy endpoints were assessed by BICR.


The overall efficacy-evaluable population comprised 172 patients with ROS1-fusion positive NSCLC who were ROS1 TKI-naïve. Of them, 67 patients had not received any prior lines of systemic therapy in the metastatic setting. Median age was 54.5 years (range 20-86), 65.7% were female, 35.5% were current or former smokers, 23.3% had received ≥2 prior lines of therapy in the metastatic setting and 34.9% had investigator-assessed baseline CNS metastases. The median duration of survival follow-up was 37.8 months. Entrectinib demonstrated robust and durable efficacy in patients with ROS1-fusion positive NSCLC, regardless of baseline CNS status. In the overall efficacy population, the ORR was 67.4%, with a median DoR of 20.4 months, a median PFS of 16.8 months and a median OS of 44.1 months. In patients who received entrectinib as first-line treatment (N= 67), the ORR was 68.7%, median DoR was 35.6 months, median PFS was 17.7 months and the median OS was 47.7 months. In patients with BICR-assessed baseline CNS metastases (N= 51), median IC-ORR was 49%, including eight patients (15.7%) with a complete response. The median IC-DoR was 12.9 months and median IC-PFS was 12.0 months. In the safety-evaluable population (N= 247), the most frequent treatment-related adverse events (TRAEs) were dysgeusia (43%), weight increase (38%), dizziness (35%), constipation (32%) and diarrhoea (30%). Most TRAEs were grade 1/2 (57%). One patient (<1%) died due to a TRAE. TRAEs leading to dose interruption, reduction and discontinuation occurred in 36%, 35% and 7% of patients, respectively.


In this updated analysis with longer follow-up and a larger patient population, entrectinib continues to demonstrate overall and intracranial efficacy and a manageable safety profile in patients with ROS1-fusion positive NSCLC.


Fan Y, Drilon A, Chiu C, et al. Entrectinib in Patients with ROS1 Fusion-Positive (ROS1-fp) NSCLC: Updated Efficacy and Safety Analysis. Presented at IASCLC WCLC2022; Abstract MA13.04.

Speaker Yun Fan

Yun Fan

Yun Fan, MD, PhD, Zhejiang Cancer Hospital, Hangzhou, China


See: Keyslides

Back to Top