Entrectinib versus crizotinib in Asian patients with ROS1-positive non-small cell lung cancer: A matching-adjusted indirect comparison

Objectives: Entrectinib and crizotinib are the only ROS proto-oncogene 1 receptor (ROS1) tyrosine kinase inhibitors available for most Asian patients. Their efficacy has neither been compared directly in clinical trials in patients with ROS1-positive non-small cell lung cancer (NSCLC), nor indirectly in Asian populations. Thus, we aimed to provide comparative evidence of the efficacy and safety of entrectinib and crizotinib for Asian patients with advanced or metastatic ROS1-positive NSCLC.

Materials and methods: Efficacy, including overall survival (OS) and progression-free survival (PFS), and safety were evaluated using an unanchored matching-adjusted indirect comparison (MAIC). Individual patient data (IPD) from entrectinib trials (ALKA-372-001/EudraCT 2012-000148-88, STARTRK-1/NCT02097810, and STARTRK-2/NCT02568267; dosage, ≥600 mg once daily; enrollment cutoff, 02 July 2020; data cutoff, 02 August 2021) and aggregate data with simulated pseudo-IPD from a crizotinib trial (OxOnc/NCT01945021; dosage, 250 mg twice daily) were analyzed. Key eligibility criteria from the crizotinib trial were applied to IPD from the entrectinib trials. Baseline characteristics were match-adjusted between arms using propensity score weighting.

Results: Fifty-two and 127 patients from the entrectinib and crizotinib trials, respectively, were available for evaluation. Median OS was not reached (NR; weighted; 95 % confidence interval [CI] 28.3-NR) in the entrectinib arm and 44.2 months (95 % CI 32.0-NR) in the crizotinib arm (hazard ratio [HR], 0.662; 95 % CI 0.32-1.37). The respective median PFS was 39.4 months (weighted; 95 % CI 10.4-46.8) and 15.9 months (95 % CI 12.9-24.0) (HR, 0.688; 95 % CI 0.37-1.27). Most AEs were Grade 1-2; both drugs were generally well tolerated. Neutropenia was the most common Grade 3 or 4 treatment-related adverse event for both entrectinib and crizotinib.

Conclusions: The outcomes in this MAIC study including Asian patients with ROS1-positive NSCLC showed a trend for greater clinical benefit with entrectinib versus crizotinib. These findings may contribute to better-informed treatment decisions.