OBJECTIVES : Entrectinib is a central nervous system (CNS)-active potent inhibitor of TRK A/B/C and ROS1 and is licensed for the treatment of patients with ROS1-positive (ROS1+) NSCLC. The current study was undertaken to identify clinical studies conducted in patients with ROS1+ NSCLC and to estimate the relative efficacy and safety of entrectinib versus crizotinib.

METHODS : A systematic literature review conducted in March 2019 was updated in March 2020. Data available for evidence synthesis included a pooled analysis of three Phase I and Phase II clinical trials for entrectinib and one trial, PROFILE 1001, for crizotinib. A MAIC based on known prognostic and predictive factors, including CNS metastases, was used to compare treatments. As the percentage of patients with CNS metastases was not reported in PROFILE 1001, this parameter was varied in scenario analyses. Outcomes included objective response rate (ORR), overall survival (OS), progression free survival (PFS), and discontinuation due to adverse events (AEs).

RESULTS : Results from the MAIC indicated a trend towards improved OS for entrectinib versus crizotinib in all three scenarios (hazard ratio (HR) ranging from 0.75 [95% confidence interval (CI) 0.46, 1.11] to 0.87 [95% CI 0.54, 1.27]). A numerical trend in favour of entrectinib was observed for discontinuation due to AEs (odds ratio (OR): 0.70 [95% CI 0.30, 1.10] to 0.70 [95% CI 0.30, 1.30]). There was no difference in ORR between treatments (OR: 0.90 [95% CI 0.60, 1.50] to 1.10 [95% CI 0.70, 1.60]). For PFS, there was a trend towards higher risk of disease progression for entrectinib versus crizotinib (HR: 1.23 [95% CI 0.89, 1.60] to 1.29 [95% CI 0.94, 1.68]).

CONCLUSIONS : Entrectinib is an effective and well tolerated treatment for patients with ROS1+ NSCLC and data from the MAIC indicate a trend towards improved OS (but not PFS) and safety with entrectinib versus crizotinib.