Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child‐Pugh class A or B liver function in real‐world clinical practice

Abstract

Background/Aim Atezolizumab plus bevacizumab (Atez/Bev) treatment is recommended for unresechepatocellular carcinoma (u‐HCC) patients classified as Child‐Pugh A (CP‐A). This study aimed to elucidate the prognosis of patients treated with Atez/Bev, especially CP‐A and ‐B cases. Materials/methods From September 2020 to March 2022, 457 u‐HCC patients treated with Atez/Bev were enrolled (median age 74 years, male:female = 368:89, CP‐A:CP‐B = 427:30, Child‐Pugh score [CPS] 5:6:7:8:9 = 271:156:21:8:1). Therapeutic response was evaluated using RECIST ver.1.1. Clinical features and prognosis were retrospectively evaluated. Results There were no significant differences between CP‐A and ‐B patients in regard to best response (CR:PR:SD:PD = 16:91:194:81 vs. 0:7:13:8, p = 0.739; objective response rate/disease control rate = 28.0%/78.8% vs. 25.0%/71.4%). Analysis performed using inverse probability weighting adjustments of clinical factors other than those related to hepatic reserve function with a p value < 0.10 for comparisons between patients with CP‐A and ‐B showed that the progression‐free survival (PFS) rate for CP‐A cases was better (6‐/12‐/18‐month: 58.2%/36.1%/27.8% vs. 49.6%/8.7%/non‐estimable [NE], p < 0.001), as was overall survival (OS) rate (6‐/12‐/18‐month: 89.9%/71.7%/51.4% versus 63.6%/18.4%/NE; p < 0.001). Median PFS (mPFS) and median OS (mOS) for the CPS‐5 were 9.5 months/NE, and 5.1/14.0 months for the CPS‐6 (both p < 0.001). Furthermore, for modified albumin‐bilirubin grade (mALBI)‐1/2a/2b, mPFS was 9.4/8.5/5.3 months (p < 0.001) and mOS was NE/17.8/13.4 months (p < 0.001). Conclusion Better hepatic function, such as mALBI grade 1 or 2a are thought to indicate a better condition for obtaining sufficient prognosis with Atez/Bev treatment for u‐HCC patients, whereas for CP‐B patients, who mainly shown an mALBI grade of 2b or 3, Atez/Bev might have less therapeutic efficacy.

Changes in ALBI Score and PIVKA-II within Three Months after Commencing Atezolizumab Plus Bevacizumab Treatment Affect Overall Survival in Patients with Unresectable Hepatocellular Carcinoma

“…The nature and severity of treatment-related AEs observed in this study differed substantially from those previously reported [ 8 , 21 , 22 , 23 , 27 , 28 , 29 , 30 , 31 ]. In contrast, we detected significant deterioration in liver functional reserve including albumin levels, Child–Pugh score, ALBI score, and the appearance of ascites within the initial 3 months of treatment.…”

“…In contrast, we detected significant deterioration in liver functional reserve including albumin levels, Child–Pugh score, ALBI score, and the appearance of ascites within the initial 3 months of treatment. Although the findings of some studies have indicated that ALBI scores tend to decline within the first few weeks of treatment, observations in most previous studies have tended to indicate that these scores do not deteriorate in response to Atez/Bev [ 23 , 27 , 29 , 30 , 31 ]. The fact that we detected a positive correlation between the ∆ ALBI score and ∆ PIVKA-II in the present study (coefficient of correlation = 0.286, p = 0.034; Figure S4 ) would tend to imply that a deterioration in the ALBI score is associated with the progression of HCC itself, rather than with the AEs of this treatment.…”

“…These latter differences could be ascribed to the larger number of enrolled patients in our study who had Child–Pugh B, had received pretreatment that included other systemic therapies, or had non-viral hepatitis. In this regard, the findings of some studies have indicated that patients with Child–Pugh B or non-viral hepatitis and those who received Atez/Bev as a later-line treatment had poorer clinical outcomes [ 13 , 22 , 23 ]. In the present study, we found that patients with Child–Pugh B had significantly poorer survival than those with Child–Pugh A ( Figure S3a ; p = 0.027), whereas there were no significant differences in OS among patients who received Atez/Bev as a first-line and later-line treatment ( Figure S3b ; p = 0.472) or patients with viral and non-viral hepatitis ( Figure S3c ; p = 0.178).…”

Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150

“…In addition, most patients had a Child-Pugh score of 7. A recent study reports that the median PFS for atezolizumab and bevacizumab is similar in patients with a Child-Pugh score of 6 (5.1 months, 95%CI: 3.8–6.4 months) and 7 (6.3 months, 95% CI: 2.3–7.0 months) [ 24 ]. This might explain the better PFS of patients with Child-Pugh B in this study; however, further studies with larger sample sizes are required to confirm this.…”

Atezolizumab plus bevacizumab for patients with Child-Pugh-B in hepatocellular carcinoma

“…The median OS (95% CI) was 7.6 (4.4–10.5) months. A retrospective study to examine the outcomes and safety of patients treated atezolizumab plus bevacizumab between CP-A (n=427) and CP-B (n=30) status has just been published ( 6 ). In terms of AEs, patients with CP-B significantly more frequently experienced appetite loss and edema/ascites than those with CP-A.…”