Table 1 shows an overview of patient characteristics. The median age of all patients was 73.0 (68.0-78.0) years and 243 patients (81.8%) were men. The PS was 0, 1, and 2 in 238 (80.1%), 49 (16.5%), and 10 patients (3.4%), respectively. The etiology of chronic liver diseases was HCV, HBV, alcohol, and others in 97 (32.7%), 49 (16.5%), 57 (19.2%), and 94 (31.6%) patients, respectively. The Child-Pugh score was 5, 6, and ≥7 in 183 (61.6%), 96 (32.3%), and 18 patients (6.1%), respectively. The median ALBI score was calculated to be -2.43 (-2.70 to -2.13) and the mALBI grades were 1, 2a, 2b, and 3 in 115 (38.7%), 76 (25.6%), 104 (35.0%), and 2 patients (0.7%), respectively. One hundred sixty-nine (56.9%) and 128 patients (43.1%) received Atez/Bev as a front line and later line treatment, respectively. The BCLC stage was classified as early, intermediate, advanced, and terminal in 17 (5.7%), 121 (40.7%), 155 (52.2%), and 4 patients (1.3%), respectively. There were 122 patients (41.1%) with a serum AFP ≥100 ng/mL and 67 patients (22.6%) with serum CRP ≥1.0 mg/dL. Accordingly, the patients were assigned CRAFITY scores of 0 (n=147 [49.5%]), 1 (n=111 [37.4%]), and 2 points (n=39 [13.1%]). The patients with a CRAFITY score of 0 points showed significantly better PS, better preservation of the liver function, a higher percentage of first-line treatment, and an earlier HCC stage in comparison to those with CRAFITY scores of 1 or 2 points.
The numbers of patients with a confirmed radiological response, as assessed by RECIST ver.1.1, are shown in Table 2. Among the patients with CRAFITY scores of 0, 1, and 2 points, 119, 101, and 37 patients, respectively, showed a confirmed radiological response. The radiological response rate (p=0.20) and ORR (p=0.80) were not significantly different, while a significant difference in the DCR was observed among the three groups (p=0.029).
The Kaplan-Meier curves showed that the median PFS was 6.8 months (95% CI 6.0-8.0), with 144 events (48.8%) detected at the time of the analysis (Figure 2a). While the median OS was not reached, the 6-month, and 12-month OS rates were 89.9% (95% CI 85.3-93.1) and 66.1% (95% CI 55.6-74.6%), respectively, with 52 events (17.5%) found at the time of the analysis (Figure 2b). The results obtained from the multivariate analysis are presented in Table 3. The following factors showed a significant association with PFS: AFP≥100 ng/mL (HR 1.97, 95% CI 1.40-2.77, p<0.001) and CRP≥1.0 mg/dL (HR 1.51, 95% CI 1.05-2.19, p=0.028). A statistical analysis of factors related to OS also revealed that AFP≥100 ng/mL (HR 2.74, 95% CI 1.52-4.92, p<0.001) and CRP≥1.0 mg/dL (HR 1.87, 95% CI 1.06-3.31, p=0.032) were predictors of OS. A multivariate analysis was performed using the CRAFITY score as an explanatory variable, and the HRs and 95% CIs of each CRAFITY score are described in Supplemental Table 1.
The PFS and OS for each CRAFITY score are shown in Figure 3. In the CRAFITY 0, 1, and 2 points groups, the median PFS was 11.8 months (95% CI 6.4-not applicable [NA]), 6.5 months (95% CI 4.6-8.0), and 3.2 months (95% CI 1.9-5.0), respectively, (p<0.001). The results of the analysis of PFS in patients with BCLC early and intermediate stage according to the CRAFITY score are shown in Supplemental Figure 2a and those of patients with BCLC advanced and terminal stage are shown in Supplemental Figure 2b. The median OS in patients with CRAFITY score 0 points was not reached while it was 14.3 months (95% CI 10.5-NA) and 11.6 months (95% CI 4.9-NA) in patients with CRAFITY scores of 1 point and 2 points, respectively. There was a significant difference among the three groups (p<0.001). The 6-month and 12-month OS rates were 94.7% (95% CI 88.4-97.6) and 81.1% (95% CI 66.1-89.9%), respectively, in patients with CRAFITY score 0, 92.9% (95% CI 85.6-96.6%) and 63.5% (48.3-75.3%) in patients with CRAFITY score 1, and 63.6% (95% CI 44.5-77.7%) and 33.2% (95% CI 10.5-58.3%) in patients with CRAFITY score 2. The survival curves for patients with BCLC early and intermediate stage, stratified by the CRAFITY score, are shown in Supplemental Figure 3a, while those with BCLC advanced and terminal stage are also shown in Supplemental Figure 3b.
A summary of AEs according to the CRAFITY score is shown in Table 4. The most common AEs in all patients was fatigue (n=75, 25.3%), followed by proteinuria (n=71, 23.9%), decreased appetite (n=70, 23.6%), hypertension (n=58, 19.5%), and liver injury (n=40, 13.5%). Significant differences were observed in grade ≥3 liver injury (p=0.036), any grade of decreased appetite (p=0.002), any grade of proteinuria (p=0.039), any grade of fever (p=0.011), and any grade of fatigue (p=0.032). The rates of these AEs were lowest in patients with a CRAFITY score of 0, followed by patients with CRAFITY scores of 1 and 2.