Atezolizumab plus Bevacizumab versus Sorafenib in the Chinese Subpopulation with Unresectable Hepatocellular Carcinoma: Phase 3 Randomized, Open-Label IMbrave150 Study

Abstract

<b><i>Introduction:</i></b> Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety data from the Chinese subpopulation are reported. <b><i>Methods:</i></b> IMbrave150, a global, randomized, open-label, phase 3 study in patients with systemic treatment-naive unresectable HCC, included an extension phase that enrolled additional patients from mainland China. Patients were randomized (2:1) to receive intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg once every 3 weeks or sorafenib 400 mg twice a day until unacceptable toxicity or loss of clinical benefit. Co-primary endpoints were OS and independent review facility-assessed PFS per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population. <b><i>Results:</i></b> Of 194 Chinese patients enrolled from April 16, 2018, to April 8, 2019 (137 in the global study and 57 in the China extension phase), 133 received atezolizumab plus bevacizumab and 61 received sorafenib. At the data cutoff (August 29, 2019), the stratified hazard ratio for OS was 0.44 (95% CI, 0.25–0.76) and for PFS was 0.60 (95% CI, 0.40–0.90). The respective median OS and PFS with atezolizumab plus bevacizumab were not reached (NR; 95% CI, 13.5 months to NR) and 5.7 months (95% CI, 4.2–8.3) versus 11.4 months (95% CI, 6.7 to NR) and 3.2 months (95% CI, 2.6–4.8) with sorafenib. Grade 3–4 adverse events (AEs) occurred in 78 of 132 (59.1%) atezolizumab plus bevacizumab-treated and 27 of 58 (46.6%) sorafenib-treated patients. The most common grade 3–4 AE with atezolizumab plus bevacizumab was hypertension, occurring in 15.2% of patients; however, other high-grade AEs were infrequent. <b><i>Conclusion:</i></b> Clinically meaningful improvements in OS and PFS observed with atezolizumab plus bevacizumab versus sorafenib suggest that atezolizumab plus bevacizumab may become a practice-changing treatment for Chinese patients with unresectable HCC.

Correlation Between Immune-Related Adverse Events and Prognosis in Hepatocellular Carcinoma Patients Treated With Immune Checkpoint Inhibitors

“…However, in the further phase III trials, no satisfying results were obtained for these two antibodies (17,18). The IMbrave150 trial combining the anti-PD-L1 antibody of atezolizumab and the anti-VEGF antibody of bevacizumab obtained a breakthrough for advanced HCC treatment referring to ORR, PFS, and OS when compared with sorafenib as the first-line treatment (19)(20)(21). In addition, the combination of lenvatinib plus pembrolizumab as a front-line treatment in advanced HCC patients is being evaluated based on its good treatment efficiency in a Phase I study (22,23).…”

Antioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1

“…Recently, some studies have provided evidence that activation of GSH production or thioredoxin system in cancer cells might exert counteractive effects on cancer treatments including chemotherapy [ 29 , 30 ], while targeting the antioxidant enzyme such as catalase could inhibit CSCs in breast cancer and improve therapeutic efficacy [ 31 ]. For advanced HCC, Sorafenib is one of the first-line drugs [ 32 ]. Of significance, in this study, both NAC and GSH could abrogate the growth-suppressive effects exerted by Sorafenib in vitro in tumor xenografts.…”

Experimental Research on the Inhibitory Effect of IFN-Lambda 3 Combined with Sorafenib on the Growth of Liver Cancer Transplanted into Nude Mice

“…For this reason, sorafenib has been included in the fast-track channel for drug approval in many countries to treat advanced or partially end-stage HCC patients. Ever since its successful clinical application in the market, sorafenib is still the preferred treatment for patients with advanced HCC that cannot be surgically resected or that is complicated with distant organ invasion and metastases, despite doubts, challenges, and the impact of various new targeted drug development [11] . Therefore, looking for a supportive treatment regimen of sorafenib to improve the survival benefit of HCC patients has become a hot topic [12] .…”