Atezolizumab-bevacizumab and Other Immunotherapies: Real-life Experience for Treatment of Hepatocellular Carcinoma

• Background Hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third leading cause of cancer-related death. In most cases (about 80%), HCC develops in a cirrhotic liver - a condition where the liver has been damaged over time, leading to scarring. This makes treatment more challenging.
• New Advances in Treatment Options

For many years, sorafenib was the only approved drug for advanced liver cancer when local treatments like surgery were not possible. However, significant advancements have changed the treatment landscape:

• Atezolizumab and Bevacizumab (Immunotherapy Combination):

In 2019, a groundbreaking study (ImBRAVE-150, Phase 3) demonstrated that combining atezolizumab (an immunotherapy drug) and bevacizumab (an anti-angiogenic drug) significantly improved disease-free survival (time without cancer worsening) and overall survival compared to sorafenib.

This combination was approved in 2019 by the European Medicines Agency (EMA) and later by the Italian Medicines Agency (AIFA) in 2022.

• Durvalumab and Tremelimumab (Dual Immunotherapy):

In February 2024, another combination-durvalumab and tremelimumab-was introduced following the results of the Phase 3 HIMALAYA trial, which also showed improved outcomes compared to sorafenib.

Several other immunotherapy-based combinations, such as camrelizumab-rivoceranib and nivolumab-ipilimumab, are under evaluation and may become available in the future.

• Why Is This Study Important?

• Real-World Effectiveness of Treatments:

While clinical trials have shown promising results for atezolizumab-bevacizumab and durvalumab-tremelimumab, real-world data-information gathered from everyday clinical practice-are still limited. In particular, there is a lack of real-world evidence for the new durvalumab-tremelimumab combination. This study aims to fill that gap by collecting and analyzing data from patients treated in daily clinical practice.

• Understanding Treatment Sequences:

After completing atezolizumab-bevacizumab or durvalumab-tremelimumab, what is the best next treatment? Currently, the only approved next-line drug is sorafenib, and for third-line treatment in Italy, cabozantinib is the only option. However, there is no clear scientific data on the effectiveness of these treatment sequences.

As more therapies become available, it will be critical to identify the best sequence of treatments to extend survival and improve quality of life.

• Identifying Predictors of Response:

Some patients respond better to treatment than others. This study seeks to identify clinical and laboratory markers that predict which patients will benefit most from specific therapies.

For example, with sorafenib, the development of certain side effects (like skin reactions) was associated with better survival. It remains unclear whether similar markers exist for newer drug combinations.

Additionally, the study will examine how factors such as treatment intolerance, patterns of disease progression, and second-line therapies influence survival outcomes.

• What This Study Aims to Achieve

This study will gather and analyze data from patients treated in real-world settings to:

• Understand the effectiveness and safety of new treatment combinations (e.g., atezolizumab-bevacizumab and durvalumab-tremelimumab).

Identify the best treatment sequences for patients with advanced liver cancer.

• Discover clinical and laboratory markers that predict treatment responses, helping personalize care and optimize outcomes.

By addressing these questions, this study will provide valuable information to healthcare providers and guide future treatment decisions for patients with liver cancer.

Inclusion criteria

• Hepatocellular carcinoma not amenable to locoregional procedures
• Candidate to frontline systemic treatment with atezolizumab-bevacizumab or other immunotherapies

Exclusion criteria

• Concurrent treatment with other antineoplastic agents
• Other active neoplasia