Combination of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma

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Combination therapy with the programmed cell death ligand 1 inhibitor atezolizumab and the vascular endothelial growth factor inhibitor bevacizumab significantly improved overall and progression-free survival in patients with unresectable hepatocellular carcinoma compared with sorafenib, according to the findings of the phase III IMbrave150 trial. These results were presented by Ann-Lii Cheng, MD, PhD, Director of the National Taiwan University Cancer Center, and colleagues at the European Society for Medical Oncology (ESMO) Asia Congress 2019 and published in the Annals of Oncology.1

This is the first study in 11 years to show an improvement in survival with a new first-line treatment option [atezolizumab plus bevacizumab] compared with sorafenib.
— Ann-Lii Cheng, MD, PhD

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“This is the first study in 11 years to show an improvement in survival with a new first-line treatment option compared with sorafenib, which has been the standard of care throughout this time,” said Dr. Cheng. “Atezolizumab plus bevacizumab has the potential to be a practice-changing treatment option in hepatocellular carcinoma. Despite many studies over the past 11 years, we have been unable to find any better treatment option. This has been very frustrating because sorafenib has a response rate of around 10% and is associated with severe side effects.”

IMbrave150 Results

The phase III IMbrave150 study randomly assigned 501 patients with unresectable hepatocellular carcinoma on a 2:1 basis to atezolizumab (1,200 mg intravenously [IV] every 3 weeks) plus bevacizumab (15 mg/kg IV every 3 weeks) or sorafenib (400 mg twice daily). The patients continued with their assigned treatment until unacceptable toxicity or loss of clinical benefit, as judged by study investigators.

Results showed a hazard ratio (HR) for overall survival of 0.58 (95% confidence interval = 0.42–0.79, P = .0006) after a median follow-up of 8.6 months. The median overall survival has not yet been reached for atezolizumab plus bevacizumab, compared with 13.2 months for patients treated with sorafenib. Median progression-free survival was also significantly increased (median 6.8 vs 4.3 months, HR = 0.59; 95% CI = 0.47–0.76, P < .0001).

The overall response rate was 27% with atezolizumab plus bevacizumab vs 12% with sorafenib (P < .0001), based on independent assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and similarly increased using hepatocellular carcinoma modified RECIST (33% vs 13%, P < .0001). Atezolizumab plus bevacizumab delayed the deterioration in quality of life compared with sorafenib.

Grade 3 or 4 adverse events occurred in 57% of patients treated with atezolizumab plus bevacizumab and 55% of those receiving sorafenib. Grade 5 adverse events occurred in 5% and 6% of patients, respectively.

Additional Commentary

Angela Lamarca, MD, PhD, Consultant Medical Oncologist at the Christie NHS Foundation Trust, commented on the findings of the IMbrave150 trial: “This is a breakthrough and based on the results, the combination of atezolizumab plus bevacizumab could become the new standard of care. The results are clinically meaningful in the setting of advanced hepatocellular carcinoma, as well as statistically significant. The delayed deterioration in quality of life is also important—patients are living longer, and their quality of life is better.”

Angela Lamarca, MD, PhD

Angela Lamarca, MD, PhD

Dr. Lamarca considered the study to be well designed with several strengths, including its large sample size, the use of a combination endpoint of progression-free and overall survival, assessment of response/disease progression by a central reviewer, and analysis based on the intention-to-treat population. Dr. Lamarca also noted that the median follow-up of 8.6 months is relatively short, with the median overall survival for atezolizumab plus bevacizumab not yet being reached. 

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1. Cheng AL, Qin S, Ikeda M, et al: IMbrave150: Efficacy and safety results from a phase 3 study evaluating atezolizumab + bevacizumab vs sorafenib as first treatment for patients with unresectable hepatocellular carcinoma. Ann Oncol. November 24, 2019 (early release online).