This multicenter study showed that the median OS and PFS were greater in patients with CP-A liver function than in patients with CP-B (score of 7–8) liver function, but these differences were not statistically significant. After PSM, the OS, PFS, ORR, and DCR of CP-A patients were comparable to those of CP-B (score of 7–8) patients. No significant difference was observed in the incidence of grade 3/4 AEs between the two groups.
HCC patients with CP-B status face a tough management challenge. Therefore, we were concerned about the efficacy of TACE combined with PD-1 inhibitors plus MTT in patients with impaired liver function. The study showed that CP-A patients didn’t achieve a remarkable survival advantage compared to CP-B (score of 7–8) patients, suggesting that CP-A patients had a comparable clinical benefit compared to CP-B (score of 7–8) patients, even though they had different CP grades and therefore had distinct prognostic weights according to the staging system used[3]. This result was probably because of the comparable PFS, ORR, as well as DCR in the CP-A and CP-B (score of 7–8) groups.
Previous studies have shown that the median OS for HCC patients with CP-B receiving sorafenib is markedly lower than that for patients with CP-A (2.5–5.4 months vs. 6.1–13.6 months).[10, 22–25] Subgroup analysis of CheckMate 040 cohort 5 including forty-nine nivolumab-treated patients showed that the median OS for CP B (score of 7–8) patients was 7.6 months (95% CI, 4.4–10.5).[26] In addition, a multicenter study of patients receiving camrelizumab plus MTT showed a median OS of 13.4 months in CP-B patients.[15] Two real-world studies revealed that CP-B patients receiving atezolizumab plus bevacizumab achieved a median OS of 6.4–6.7 months.[27, 28] The median OS of CP-B (score of 7–8) patients in our study was significantly greater than that in previous studies, suggesting that TACE combined with PD-1 inhibitors plus MTT might benefit patients with CP-B (score of 7–8). This study provides an alternative treatment option for unresectable HCC patients with CP-B (score of 7–8) liver function, who are frequently excluded from receiving immunotherapy and/or targeted therapy in clinical practice.
In this study, the PFS, ORR, and DCR of CP-A patients were comparable to those of CP-B (score of 7–8) patients. Previous studies estimating the combination of atezolizumab and bevacizumab for unresectable CP-B HCC patients showed a PFS of 3.4-6.0 months, an ORR of 21%-25%, and a DCR of 68%-71.4%, which were remarkably shorter than those for CP-B (score of 7–8) patients in the present study.[27, 28] The possible reasons for these results were as follows: first, the addition of TACE to PD-1 inhibitors plus MTT enables a rapid reduction in the tumor load. Second, super-selective TACE increases the susceptibility of tumors to necrosis. Finally, the synergistic effect of TACE, which leads to antigen release from necrotic tumor cells and elevated vascular endothelial growth factor, combined with PD-1 inhibitors plus MTT could improve tumor shrinkage.
Safety was an important concern in our study. Overall, TACE combined with PD-1 inhibitors plus MTT therapy for unresectable HCC in CP-B (score of 7–8) patients led to 21.7% grade 3/4 AEs, similar to the results in CP-A patients (13.1%), and no new safety concerns were encountered. In addition, as with previous reports on two-drug combinations, TACE combined with PD-1 inhibitors plus MTT led to similar AEs.[29–31] Notably, CP-B (score of 7–8) patients were at greater risk of discontinuing treatment due to deterioration of liver function.
This study had several limitations. First, the retrospective nature of the study had inherent biases. Second, the relatively small sample size had the possibility of selection bias. Finally, the types of PD-1 inhibitors and MTT drugs are diverse, which might influence the outcome of the study.