Overall survival (OS) of patients with TRK fusion–positive cancer receiving larotrectinib versus standard of care (SoC): A matching-adjusted indirect comparison (MAIC) using real-world data (RWD).

Abstract

6579 Background: Larotrectinib trials in Tropomyosin Receptor Kinase (TRK) fusion cancer population were single arm trials and therefore limited comparative effectiveness data with larotrectinib are available.MAIC is typically used to balance population characteristics to facilitate cross-study comparisons. The objective of this study was to use MAIC to compare efficacy of the highly specific TRK inhibitor larotrectinib vs. SoC. Methods: Individual patient data from larotrectinib trials (NCT02122913, NCT02637687, NCT02576431) were compared with published aggregate SoC data from patients with locally advanced/metastatic TRK fusion cancer identified in the Flatiron Health/Foundation Medicine clinico-genomic database (Demetri et al. Ann Oncol. 2021). Prior to matching, eligible patients were ≥18 years and had to have received ≤4 lines of prior therapy (LoPT). Patients were matched on available common baseline characteristics (Table). Overall survival was the only endpoint assessed and was defined as time from locally advanced/metastatic disease diagnosis to death. The analyses included: 1) a log-rank test of equality to test whether the two groups were similar before larotrectinib initiation; and 2) estimation of treatment effect of larotrectinib vs. SoC. Hazard ratios (HRs) were used to compare the 2 groups. MAIC assumes that all observed and unobserved prognostic factors are adjusted for in the analysis. Results: 85 larotrectinib patients and 28 SoC patients were included. After matching, log-rank testing suggested no difference between the 2 groups (P=0.26), and larotrectinib was associated with a 78% lower risk of death (adjusted HR: 0.22 [95% confidence interval: 0.09, 0.54]; P=0.001), compared to SoC. Conclusions: This analysis suggests longer overall survival with larotrectinib, compared to SoC, in adult patients with TRK fusion cancer. The current analysis was limited to the prognostic variables available in the RWD. Further data are warranted to confirm those results. [Table: see text]