Liver and Bile
J Hepatol. 2022;76(2):353–63
Prognosis of patients with hepatocellular carcinoma treated with immunotherapy – Development and validation of the CRAFITY score
Background and aims: Immunotherapy with atezolizumab plus bevacizumab represents the new standard of care in systemic front-line treatment of hepatocellular carcinoma (HCC). However, biomarkers that predict treatment success and survival remain an unmet need.
Methods: Patients with HCC put on PD-(L)1-based immunotherapy were included in a training set (n = 190; 6 European centers) and a validation set (n = 102; 8 European centers). The authors investigated the prognostic value of baseline variables on overall survival using a Cox model in the training set and developed the easily applicable CRAFITY (CRP and AFP in ImmunoTherapY) score. The score was validated in the independent, external cohort, and evaluated in a cohort of patients treated with sorafenib (n = 204).
Results: Baseline serum alpha-fetoprotein ≥ 100 ng/ml (hazard ratio [HR] = 1.7; p = 0.007) and C-reactive protein ≥ 1 mg/dl (HR = 1.7; p = 0.007) were identified as independent prognostic factors in multivariable analysis and were used to develop the CRAFITY score. Patients who fulfilled no criterion (0 points; CRAFITY-low) had the longest median overall survival (27.6 months [95% CI: 19.5–35.8]), followed by those fulfilling 1 criterion (1 point; CRAFITY-intermediate; 11.3 months [95% CI: 8.0–14.6]), and patients meeting both criteria (2 points; CRAFITY-high; 6.4 months [95% CI: 4.8–8.1]; p < 0.001). Additionally, best radiological response (complete response/partial response/stable disease/progressive disease) was significantly better in patients with lower CRAFITY score (CRAFITY-low: 9%/20%/52%/20% vs. CRAFITY-intermediate: 3%/25%/36%/36% vs. CRAFITY-high: 2%/15%/22%/61%; p = 0.003). These results were confirmed in the independent validation set and in different subgroups, including Child-Pugh A and B, performance status 0 and ≥ 1, and first-line and later lines. In the sorafenib cohort, CRAFITY was associated with survival, but not radiological response.
Conclusions: The CRAFITY score is associated with survival and radiological response in patients receiving PD-(L)1 immunotherapy. The score may help with patient counseling but requires prospective validation.