Lenvatinib Versus Atezolizumab Plus Bevacizumab as First‐Line Treatment for Advanced Hepatocellular Carcinoma With a CRAFITY Score of 2: A Multi‐Center Retrospective Study

AIM: Atezolizumab plus bevacizumab (Atezo+Bev) therapy is the preferred first-line treatment for advanced hepatocellular carcinoma (HCC). However, the efficacy of Atezo+Bev is limited in patients with a CRAFITY score of 2 (C-reactive protein ≥ 1 mg/dL and alpha-fetoprotein [AFP] ≥ 100 ng/mL). This study compared the efficacy and safety of lenvatinib and Atezo+Bev in these patients. METHODS: We retrospectively analyzed 774 patients treated with lenvatinib or Atezo+Bev as first-line treatment for advanced HCC between October 2020 and December 2023 across 11 hospitals in Japan. Among them, 90 patients (11.6%) had a CRAFITY score of 2. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety profiles were compared. RESULTS: Baseline characteristics were similar, except tumor size and AFP levels, which were higher in the Atezo+Bev group. Median PFS was significantly longer in the lenvatinib group compared to the Atezo+Bev group (6.0 vs. 2.3 months; hazard ratio [HR]: 0.55, 95% confidence interval [CI]: 0.32-0.95]; p = 0.032). The median OS was not significantly different between the two groups (9.8 vs. 5.2 months; HR: 0.66, 95% CI: 0.41-1.08; p = 0.101). The DCR (62.0% vs. 30.0%; p = 0.003) and the occurrence of grade ≥ 3 treatment-related adverse events (46.0% vs. 20.0%; p = 0.014) were significantly higher in the lenvatinib group than in the Atezo+Bev group. CONCLUSION: Lenvatinib provided a significantly longer PFS than Atezo+Bev in patients with HCC and a baseline CRAFITY score of 2, whereas OS did not significantly differ between the two groups. These findings may serve as a cornerstone for developing biomarker-based strategies in first-line treatment selection for this patient population.