Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study

Abstract

<b><i>Introduction:</i></b> Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear. <b><i>Methods:</i></b> This multinational, multicenter, and retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab between July 2016 and April 2019. <b><i>Results:</i></b> Among 71 patients treated with atezolizumab-bevacizumab, a total of 49 patients who received subsequent systemic therapy were included in this analysis; the median age was 60 years (range, 37–80) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib (<i>n</i> = 29), lenvatinib (<i>n</i> = 19), and cabozantinib (<i>n</i> = 1), were used as second-line therapy for all patients. The objective response rate and disease control rate were 6.1 and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.8–4.9) and 14.7 months (95% CI 8.1–21.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 vs. 2.5 months; <i>p</i> = 0.004), although there was no significant difference in median OS (16.6 vs. 11.2 months; <i>p</i> = 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome (<i>n</i> = 26, 53.1%), fatigue (<i>n</i> = 14, 28.6%), hypertension (<i>n</i> = 14, 28.6%), and diarrhea (<i>n</i> = 12, 24.5%). <b><i>Conclusion:</i></b> Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.