OBJECTIVES : Entrectinib is an oral, systematic, and central nervous system (CNS) active inhibitor of TRK A/B/C and ROS1. The objective of this study was to identify published literature on treatments for patients with ROS1-positive NSCLC and estimate the relative efficacy and safety of entrectinib compared to crizotinib.

METHODS : A systematic literature review was performed to identify relevant studies. Data available for evidence synthesis included a pooled analysis of one Phase I and two Phase II clinical trials for entrectinib and a single trial, PROFILE 1001, for crizotinib. Matching adjusted indirect treatment comparison (MAIC) was used to perform the indirect treatment comparison, as data came from single arm clinical trials. Matching was based on known prognostic and predictive factors: age, sex, smoking status, line of treatment, ECOG performance status, and CNS metastases. Because the percentage of patients with CNS metastases was unknown in the comparator trial, three scenario analyses were performed in which this percentage was varied. Outcomes included objective response rate (ORR), overall survival (OS), progression free survival (PFS), and discontinuation due to adverse events.

RESULTS : Entrectinib was found to have significantly better objective response rates compared to crizotinib in all three scenarios (odds ratio ranging from 2.43 [95% confidence interval (CI) 1.37, 8.57] to 2.74 [95% CI 1.22, 7.02]). A numerical trend in favour of entrectinib was observed for overall survival (hazard ratio: 0.47 [95% CI 0.11, 1.03] to 0.61 [95% CI 0.16, 1.27]) and discontinuation due to adverse events (odds ratio: 0.79 [95% CI 0.29, 1.44] to 0.90 [95% CI 0.23, 1.91]). For progression-free survival, there was no evidence of a difference between treatments, except for one scenario (HR: 0.94 [95% CI 0.53, 1.43] to 1.54 [95% CI 1.06, 2.11]).

CONCLUSIONS : Several MAIC scenario analyses suggest improved outcomes for entrectinib versus crizotinib.