Atezolizumab and Bevacizumab Combination Therapy in Unresectable Hepatocellular Carcinoma

Atezolizumab, an anti-PD-L1 antibody, combined with bevacizumab, an anti-VEGF agent, has emerged as the first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). By simultaneously unleashing antitumour T-cell responses and normalising tumour vasculature, this dual approach achieved unprecedented improvements in overall survival and progression-free survival compared with previous standards. Landmark trials demonstrated objective response rates of around 30% and durable disease control while preserving hepatic function in a broad spectrum of patients, including those with advanced cirrhosis and diverse aetiologies. The regimen’s global approval has transformed treatment algorithms, enabling multidisciplinary strategies such as curative conversion in select responders. Real-world data have confirmed the safety profile observed in pivotal trials, although risks of bleeding and hypertension require vigilant monitoring. Current research focuses on refining patient selection through biomarkers, understanding resistance mechanisms, and optimising sequencing with locoregional and subsequent systemic therapies. This combination therapy represents a paradigm shift, offering renewed hope for a disease that has historically carried limited systemic options and poor prognoses.

Research from Nature Portfolio

Recent studies have uncovered that patients with non-alcoholic steatohepatitis (NASH)-driven HCC accumulate exhausted CD8+PD-1+ T cells that impair tumour immune surveillance. Preclinical models show that checkpoint blockade alone fails to induce tumour regression in NASH-HCC, and in some settings may even exacerbate disease. These findings emphasise the importance of targeting both immunosuppressive microenvironments and angiogenic pathways, thereby providing a strong rationale for combining PD-L1 inhibition with VEGF blockade. Such mechanistic insights have informed the design of newer trials seeking to overcome resistance in non-viral HCC subgroups.

Atezolizumab and Bevacizumab Combination Therapy in Unresectable Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in atezolizumab and bevacizumab combination therapy in unresectable hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Atezolizumab: a monoclonal antibody that inhibits PD-L1, enhancing T-cell-mediated antitumour immunity.

Bevacizumab: a monoclonal antibody targeting VEGF, blocking angiogenesis and normalising tumour vasculature.

Objective response rate: the proportion of patients whose tumours shrink by a predefined amount.

Progression-free survival: the time during which a patient’s disease does not worsen under therapy.

Neutrophil-to-lymphocyte ratio: a blood-based biomarker reflecting systemic inflammation and potential response to treatment.

References

1. Atezolizumab/bevacizumab or lenvatinib in hepatocellular carcinoma: Multicenter real-world study with focus on bleeding and thromboembolic events. JHEP Reports (2024).
2. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature (2021).
3. Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers. Cancers (2022).
4. Pretreatment Neutrophil-to-Lymphocyte Ratio as a Predictive Marker of Response to Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma. Current Oncology (2021).
5. The impact of curative conversion therapy aimed at a cancer‐free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Cancer Medicine (2023).
6. Changing the Treatment Paradigm for Hepatocellular Carcinoma Using Atezolizumab plus Bevacizumab Combination Therapy. Cancers (2021).