Is Toripalimab (generic name) recommended as a first-line treatment for Hepatocellular Carcinoma (HCC)?

Toripalimab in Hepatocellular Carcinoma (HCC)

Toripalimab is not currently recommended as a first-line treatment for hepatocellular carcinoma in established Western clinical guidelines, though emerging evidence shows promising results when combined with bevacizumab. Based on current guidelines, atezolizumab plus bevacizumab remains the preferred first-line systemic therapy for advanced HCC.

Current First-Line Treatment Recommendations for Advanced HCC

Standard of Care

• Atezolizumab plus bevacizumab is the first-choice standard of care for advanced HCC based on superior efficacy compared to sorafenib 1
• This combination is recommended for patients with:
  • Well-preserved liver function (Child-Pugh A)
  • Good performance status (ECOG 0-1)
  • No contraindications to either drug 1

Alternative First-Line Options

For patients who have contraindications to atezolizumab plus bevacizumab:

• Sorafenib is recommended for patients with advanced HCC and those with intermediate-stage disease not eligible for locoregional therapies 1
• Lenvatinib is an alternative first-line option showing non-inferiority to sorafenib 1

Emerging Evidence for Toripalimab in HCC

Recent research on toripalimab for HCC shows promising results:

1. Toripalimab plus bevacizumab vs. sorafenib (HEPATORCH trial) 2:

   • Significantly improved progression-free survival (5.8 vs 4.0 months)
   • Significantly improved overall survival (20.0 vs 14.5 months)
   • Acceptable safety profile

2. Toripalimab plus bevacizumab (Phase II trial) 3:

   • Objective response rate of 31.5% per RECIST v1.1
   • Median progression-free survival of 8.5 months
   • 24-month overall survival rate of 63.5%

3. Other combination approaches:

   • Lenvatinib + toripalimab + HAIC showed promising activity in high-risk advanced HCC 4, 5
   • Anlotinib + toripalimab showed an objective response rate of 29.0% and median PFS of 11.0 months 6

Important Considerations

Patient Selection

• Patients should have:
  • Well-preserved liver function (Child-Pugh A)
  • Good performance status (ECOG 0-1)
  • No untreated or inadequately treated esophageal varices (for bevacizumab-containing regimens) 1

Safety Considerations

• Most common grade ≥3 adverse events with toripalimab plus bevacizumab include:
  • Hypertension (16%)
  • Thrombocytopenia (10%)
  • Upper gastrointestinal hemorrhage (6%) 2
• Patients require endoscopic evaluation and treatment of esophageal varices before starting bevacizumab-containing regimens 1

Current Guideline Status

Despite promising results, toripalimab is not yet included in Western clinical guidelines for HCC:

• The 2024 British Society of Gastroenterology guidelines recommend atezolizumab plus bevacizumab as first-line therapy 1
• The 2022 AGA clinical practice guideline recommends atezolizumab plus bevacizumab as first-line therapy 1
• The 2018 ESMO guidelines (published before toripalimab data) recommend sorafenib or lenvatinib 1

Conclusion

While toripalimab (particularly in combination with bevacizumab) shows promising efficacy in recent clinical trials for advanced HCC, it has not yet been incorporated into major Western clinical guidelines. The combination of atezolizumab plus bevacizumab remains the recommended first-line systemic therapy for advanced HCC with well-preserved liver function. Patients who have contraindications to this regimen may receive sorafenib or lenvatinib as alternative first-line options.