Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study
Changhoon Yoo, Jwa Hoon Kim, Min‐Hee Ryu, Sook Ryun Park, Danbi Lee, Kang Mo Kim, Ju Hyun Shim, Young‐Suk Lim, Han Chu Lee, Joycelyn Jie Xin Lee, David Tai, Stephen L. Chan, Baek‐Yeol Ryoo
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.