Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab

Abstract

Background and AimsAtezolizumab/bevacizumab (A/B) is now a standard first-line (1L) treatment for advanced hepatocellular carcinoma (aHCC), but the optimal second-line (2L) regimen is not known. We evaluated real world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS). MethodsIn this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with aHCC who progressed on 1L A/B. The primary outcome of PPS was defined as time from first radiographic progression on A/B to death. Results406 patients alive after progression on 1L A/B were included in the final analysis. 45.3% (n=184) received best supportive treatment (BST) and 54.7% (n=222) continued active systemic treatment. In the 2L, 155 patients were treated with tyrosine kinase inhibitors (TKIs), 45 with immune checkpoint inhibitor (IO)-based regimens, and 3 had missing data. Median PPS of the whole cohort (mPPS) was 6.0 months (95% CI: 5.2-7.2). On multivariate Cox regression analysis, absence of portal vein tumor thrombus, ECOG <2, and continued active treatment were predictors of better PPS. mPPS was significantly longer for patients who continued active treatment versus BST (9.7 vs 2.6 months; HR 0.41, p<0.001). In the 2L setting, patients treated with TKIs had a numerically shorter mPPS compared to those treated with IO (8.4 vs 14.9 months; HR 1.37, p=0.256). ConclusionsContinuation of active therapy after A/B progression was independently associated with better survival even after adjusting for baseline disease characteristics. mPPS with IO-based therapy exceeded a year, suggesting that IO continuation post-progression may retain benefit. The precise sequencing of TKI and IO regimens warrants further investigation.