Baseline ALBI score and early variation of serum AFP predicts outcomes in patients with HCC treated by atezolizumab–bevacizumab

Abstract

Background The combination of atezolizumab and bevacizumab (AtezoBev) is the current first‐line treatment for patients with hepatocellular carcinoma (HCC). Our aim was to evaluate the prognostic role of alpha‐foetoprotein (AFP) early response and its combination with albumin–bilirubin (ALBI) in these patients. Methods Patients with HCC under AtezoBev with AFP > 20 ng/ml were included in three centres. The optimal threshold of AFP variation after 3 weeks of treatment was identified for overall survival (OS) and radiological response (RR) using RECIST 1.1 and mRECIST and its ability to predict progression‐free survival (PFS) and OS was tested using univariate and multivariate analysis in derivation and validation cohorts. Results Seventy‐five patients with AFP values >20 ng/ml were included. Fifty‐eight patients were male with a median age of 63.5 years; 73% had cirrhosis and HCC stage was classified as BCLC B (18.7%) or C (81.3%). In the derivation cohort (n = 38), a decline in AFP ≥ 20% at 3 weeks (AFP early response) was associated with RR using mRECIST criteria (OR: 13.09 95% CI: 1.44–19.34 p = .02), PFS (HR: 0.42; 95% CI: 0.19–0.93, p = .03) and OS (HR: 0.35; 95% CI: 0.15–0.83, p = .01). AFP early response was confirmed as predictor of RR (p = .02 for mRECIST) and OS (p = .03) in the validation cohort (n= 37). In the whole cohort, the combination of ALBI and AFP early response was significantly associated with OS (p = .046) and PFS (p = .012) with a poor prognosis in patients belonging to the ALBI2‐AFP non‐responders class. Conclusion AFP early response at 3 weeks predicts oncological outcomes in HCC patients treated with AtezoBev and combination with ALBI grade refines prognostic discrimination.

The combination of ALBI and AFP response: A small step forward in HCC

“…The current study not only confirms the above role of AFP response but also suggests that AFP response determined at an earlier timepoint (i.e. 3 weeks after treatment) to be clinically relevant during treatment with Atezo‐Bev 1 . This finding is potentially relevant to clinicians because it provides an early signal of response before radiological assessments, which are typically conducted after 3–4 cycles of treatment.…”

“…However, two observations from the current paper may cast concern over the routine use of early AFP response in Atezo‐Bev treatment. First, AFP responders occur in a small proportion of patients with radiologically progressive disease as shown by the supplementary figure 2 of the paper 1 . Second, the Kaplan–Meier survival curves in figure 2 of the paper indicate that there are long‐term survivors amongst the AFP‐non‐responders 1 .…”

“…For another two groups of patients, namely the ALBI grade 1‐AFP non‐responders and ALBI grade 2‐AFP responders, the interpretation is less clear. According to the survival curves of figure 3A of the paper, there is a plateau of survival during the early phase but with a rapid drop at a later timepoint for the ALBI grade 1‐AFP non‐responders, whilst the survival curve of the latter group continues to drop at a steady rate along treatment course 1 . However, because of the small sample sizes, this observation needs to be further evaluated in future studies.…”

“…Therefore, how to identify responders during the early course of treatment has been a priority research area in HCC. In this issue of Liver International , Campani et al report a multi‐centred study on developing a novel prognostic strategy for patients treated with atezolizumab and bevacizumab (Atezo‐Bev), by combining both early alpha‐fetoprotein (AFP) response and the albumin‐bilirubin (ALBI) grade 1 . Their study demonstrates that a decline of serum AFP levels ≥20% after 3 weeks of Atezo‐Bev is associated with radiological response and overall survival (OS).…”

Assessment of Liver Regeneration in Patients Who Have Undergone Living Donor Hepatectomy for Living Donor Liver Transplantation

“…We previously found that the total bilirubin was an important factor in determining the prognosis of the patient’s acute liver failure who has undergone liver transplantation [ 21 ]. Studies have shown that the bilirubin levels are indicative of the function of the liver and it is correlated with the severity of liver dysfunction [ 22 , 23 ]. In the present study, we found that the total bilirubin levels of the right-lobe liver grafts have been significantly higher than the other liver grafts which may be related with the larger mass of the liver removed and the associated decrease in the function initially observed in LLDs.…”