New clinical trial results suggest that patients with advanced liver cancer who progress after first-line immunotherapy may benefit from lenvatinib treatment. The findings, presented at the 2024 ESMO Asia Congress, mark the first prospective study examining lenvatinib's efficacy following atezolizumab plus bevacizumab therapy.
Key Clinical Outcomes
The phase 2 KCSG HB23-04 study enrolled 50 patients with advanced hepatocellular carcinoma (HCC) who had progressed after initial treatment with atezolizumab plus bevacizumab. Treatment with lenvatinib achieved a median progression-free survival (PFS) of 5.4 months (95% CI, 5.3-5.6), successfully meeting the study's primary endpoint.
The objective response rate reached 12%, with all responding patients achieving partial responses. Notably, 72% of patients maintained stable disease, resulting in an impressive disease control rate of 84%. While overall survival data remain immature, preliminary analysis shows a median of 8.6 months, with follow-up continuing.
Safety Profile
The treatment demonstrated a manageable safety profile consistent with previous lenvatinib studies. Common treatment-related adverse effects included:
- Diarrhea (32% all grades)
- Hypothyroidism (30% all grades)
- Anorexia (30% all grades)
- Hypertension (22% all grades)
Dr. Changhoon Yoo from the University of Ulsan College of Medicine emphasized that "no new safety signals were observed in patients previously treated with atezolizumab plus bevacizumab."
Study Design and Patient Population
The multicenter, single-arm trial included patients who had:
- Progressed after at least two cycles of atezolizumab/bevacizumab
- Child-Pugh class A liver function
- ECOG performance status of 0 or 1
- At least one measurable lesion
The median patient age was 66 years, with 82% being male. Most patients (70%) had viral hepatitis B as the underlying cause, and 76% presented with Barcelona-Clinic Liver Cancer stage C disease.
Clinical Implications
This study addresses a critical gap in the treatment landscape for HCC, where immune checkpoint inhibitor combinations have become standard first-line therapy. "Lenvatinib may be considered a treatment option after frontline atezolizumab/bevacizumab," stated Dr. Yoo, highlighting the potential impact on clinical practice.
The trial continues with final analysis planned for June 1, 2025, which will provide more mature survival data and longer-term safety information. These results could help establish lenvatinib as a standard second-line option for patients who progress after immunotherapy-based treatment.
