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

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. 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. 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. 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.