OBJECTIVES:

STRIDE and A+B demonstrated superiority vs sorafenib (S) for overall survival (OS), with median follow-up times of 33.2m and 15.6m, respectively. As there are no trials comparing these two regimens, this analysis estimated the comparative efficacy and safety of STRIDE vs A+B, based on the HIMALAYA and IMbrave 150 clinical trials.

METHODS:

An anchored MAIC, adjusting for aetiology, macrovascular invasion, geographical region and extrahepatic spread was completed. The primary endpoint was OS. Secondary endpoints included objective response rate (ORR), Grade 3/4 treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. A piecewise (PW) analysis was conducted for OS given the potential of non-proportional hazards over time.

RESULTS:

After reweighting to balance baseline characteristics between trials, the effective sample size for STRIDE and S was 514. No significant differences were found between STRIDE and A+B for OS (HR[95% CI]=1.09[0.80,1.48]). The PW HR from 0-9m was 1.19 (95% CI [0.76,1.87]) and 0.96 [0.61,1.51] between 9m and 26.9m (the maximum length of follow up for S in IMbrave150). The ORR odds ratio (OR) was 1.18 [95% CI: 0.44,3.21]). For safety, the OR for Grade 3/4 TEAEs was 0.73 [95% CI: 0.44,1.19]) and the OR for AE leading to discontinuation was 0.49 [95% CI: 0.23,1.04]).

CONCLUSIONS:

STRIDE was associated with similar OS and ORR as A+B. In addition, the PW HR for OS was similar between 9m and 26.9m, the timeframe in which medians were established in each trial. However, a comparison of the long-term OS benefit was not possible due to the limited duration of follow-up and maturity of IMbrave150. STRIDE was associated with fewer Grade 3/4 TEAEs and TEAEs leading to discontinuations was halved. STRIDE is the only treatment with three-year survival data that demonstrates a sustained treatment effect with a tolerable safety profile.