What is the first line immunotherapy for Hepatocellular Carcinoma (HCC)?

From the Guidelines

The first-line immunotherapy for hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab, as it has shown superiority over sorafenib in patients with preserved liver function and advanced HCC. This combination is administered intravenously with atezolizumab at 1200 mg and bevacizumab at 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity, as demonstrated in the IMBrave150 trial 1. Before starting treatment, patients should undergo endoscopic screening for varices and receive appropriate management if varices are found, as bevacizumab increases bleeding risk. Patients should also have adequate liver function (Child-Pugh A), good performance status, and no contraindications to immunotherapy such as autoimmune disorders.

The rationale behind this recommendation is based on the results of the IMBrave150 trial, which excluded individuals with a history of autoimmune diseases, allogeneic stem cell or solid organ transplantation, idiopathic pulmonary fibrosis or pneumonitis, co-infection with hepatitis B or hepatitis C viruses, and untreated or incompletely treated esophageal or gastric varices with bleeding or high risk for bleeding 1. The trial demonstrated that the combination of atezolizumab and bevacizumab improved overall survival and progression-free survival compared to sorafenib in patients with advanced HCC and preserved liver function.

Key considerations for the use of atezolizumab plus bevacizumab include:

• Endoscopic evaluation and treatment for esophageal varices before treatment to minimize the risk of gastrointestinal bleeding
• Adequate liver function, as indicated by a Child-Pugh score of A
• Good performance status, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• No contraindications to immunotherapy, such as autoimmune disorders
• Close monitoring for adverse effects, including bleeding and immune-related adverse events.

From the FDA Drug Label

1. 3 Hepatocellular Carcinoma LENVIMA is indicated for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).
2. 5 Recommended Dosage for Hepatocellular Carcinoma (HCC) The recommended dosage of LENVIMA is based on actual body weight: 12 mg for patients greater than or equal to 60 kg or 8 mg for patients less than 60 kg. Take LENVIMA orally once daily until disease progression or until unacceptable toxicity.

First-line immunotherapy for HCC is not explicitly mentioned in the label, however, LENVIMA is indicated for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).

• The recommended dosage of LENVIMA for HCC is based on actual body weight:
  • 12 mg for patients greater than or equal to 60 kg
  • 8 mg for patients less than 60 kg
  • Take LENVIMA orally once daily until disease progression or until unacceptable toxicity 2.

From the Research

First-Line Immunotherapy for HCC

• The use of immunotherapy as a first-line treatment for hepatocellular carcinoma (HCC) has been explored in several studies 3, 4, 5, 6.
• According to a 2018 study, immunotherapeutics such as nivolumab and pembrolizumab have shown promising efficacy in therapy-naïve and pre-treated patients with advanced HCC 3.
• A 2020 review discussed the role of immunotherapy in the management of HCC, highlighting the potential of combination therapies including different immunotherapeutics and small molecules 4.
• A 2022 study investigated the efficacy and safety of lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable HCC, showing a high disease control rate and stable Albumin-Bilirubin (ALBI) score 5.
• A 2024 systematic review and network meta-analysis compared first-line treatments for advanced HCC, suggesting that hepatic artery infusion chemotherapy with oxaliplatin plus fluorouracil (HAIC-FO) may be a potential first-line treatment option, while immune-related treatments may be more suitable for Asian populations 6.

Combination Therapies

• Combination therapies, such as ipilimumab and nivolumab/pembrolizumab, have been explored for patients with advanced HCC who have progressed on prior immune checkpoint inhibitors 7.
• The combination of atezolizumab and bevacizumab has shown a highly significant survival benefit and is considered a preferred standard of care in first-line therapy for HCC 4.
• Lenvatinib plus pembrolizumab has also shown promising results in patients with unresectable HCC, with a high disease control rate and stable ALBI score 5.

Patient Selection

• Patient selection is crucial for immunotherapy, with factors such as Child-Pugh class, Albumin-Bilirubin (ALBI) grade, and prior treatment history influencing treatment outcomes 7, 5.
• A 2022 study found that prior nivolumab failure was a significant factor associated with poorer progression-free survival and overall survival in patients treated with lenvatinib plus pembrolizumab 5.