Atezolizumab Plus Bevacizumab Versus Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma Stratified by the CRAFITY Score: An International Multicenter Study

Introduction: Atezolizumab plus bevacizumab (Atezo+Bev) is the most widely used first-line treatment for unresectable hepatocellular carcinoma (HCC), while lenvatinib remains a standard alternative. Previous studies suggest limited efficacy of Atezo+Bev in patients with HCC exhibiting a CRAFITY score of 2 (CRP ≥1 mg/dL and AFP ≥100 ng/mL). We conducted an international collaborative study to compare the efficacy of Atezo+Bev and lenvatinib stratified by the baseline CRAFITY score. Methods: We retrospectively analyzed 994 patients who initiated Atezo+Bev or lenvatinib as first-line therapy for unresectable HCC between September 2017 and March 2024 across 11 hospitals in Japan and 13 hospitals in Taiwan. Patients were categorized by baseline CRAFITY score, and progression-free survival (PFS) and overall survival (OS) were compared between treatment groups. Results: The median age of the patients was 71 years, and 770 (77.5%) were male. The baseline CRAFITY score was 0 in 375 patients (37.7%), 1 in 402 patients (40.4%), and 2 in 217 patients (21.8%). In patients with a CRAFITY-0 score, median PFS (10.8 vs. 9.4 months; p = 0.548) and OS (21.1 vs. 29.3 months; p = 0.074) did not differ significantly between Atezo+Bev and lenvatinib. Similar findings were observed in CRAFITY-1 patients, with median PFS of 6.0 vs. 6.1 months (p = 0.943) and OS of 12.7 vs. 15.1 months (p = 0.168). In contrast, among CRAFITY-2 patients, lenvatinib was associated with significantly longer PFS (2.3 vs. 4.4 months; hazard ratio, 0.66; p = 0.017), while OS did not differ significantly between treatments (5.7 vs. 9.1 months; hazard ratio, 0.90; p = 0.586). A significant interaction was observed between CRAFITY score (0/1 vs. 2) and treatment regimen (Atezo+Bev vs. lenvatinib) for PFS (p = 0.002). Consistent findings were observed in adjusted analyses. Conclusion: Lenvatinib was associated with significantly longer PFS than Atezo+Bev in patients with a baseline CRAFITY score of 2. The CRAFITY score may be useful for identifying patients in whom lenvatinib could be considered as a first-line option, and prospective validation is warranted.