Atezolizumab plus bevacizumab in Child-Pugh B advanced hepatocellular carcinoma patients.

Abstract

397 Background: Atezolizumab plus bevacizumab (Ate/Bev) demonstrated promising efficacy and safety in patients with advanced hepatocellular carcinoma (aHCC) in the phase III IMbrave 150 trial. However, despite the high unmet need in Child-Pugh B patients, this subgroup of patients was not included in this study. Therefore, we aimed to investigate the efficacy and safety of Ate/Bev in Child-Pugh B HCC patients. Methods: This multicenter retrospective study included 27 HCC patients classified as Child-Pugh B who received Ate/Bev at four cancer referral centers between May 2020 and August 2021. Comparative analyses were performed with an independent cohort of Child-Pugh A patients from the same registry (n=130). Results: All patients received Ate/Bev as first-line systemic treatment for aHCC. The objective response rates of patients in Child-Pugh groups B and A were 14.8% and 32.3%, and the disease control rates were 55.5% and 76.1%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.0 months (95% CI, 1.6-4.3) and 6.0 months (95% CI, 4.9-7.0) in Child-Pugh B patients, while the median PFS was 6.0 months (95% CI, 4.6-13.4) and the median OS was not-reached (95% CI not available) in Child-Pugh A group. Compared to Child-Pugh A group, grade 3-4 adverse events (AEs) were more common in the Child-Pugh B group (48.1% vs 17.7%, p=0.001), with the most frequent grade 3-4 AEs being thrombocytopenia (11.1%) and AST elevation (11.1%). The rate of treatment discontinuation due to AEs was higher in the Child-Pugh B group (14.8% vs 3.1%, p=0.030), and the reasons for discontinuation were gastrointestinal (GI) bleeding (n=2), GI perforation (n=1) and interstitial pneumonitis (n=1). Conclusions: In the Child-Pugh B subgroup of patients with aHCC, Ate/Bev treatment showed modest clinical activity. However, due to the increased frequency of serious AEs, careful evaluation of treatment response and AE management is required in this subgroup patients. [Table: see text]

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

“…In the present study, there were no obviously different clinical features, ORR/DCR and AE profiles, except for maximum intrahepatic tumor size (≥5 cm) ( p = 0.048), appetite loss and edema/ascites between the CP‐A and ‐B groups, though the mPFS and mOS time periods for the CP‐B patients were not sufficient (6.0 and 6.4 months, respectively). Similar results have been reported by Kim (mPFS/mOS = 2.9/6.0 months, n = 37) 36 and D'Alessio (mPFS/mOS = 2.3/6.5 months, n = 18) 37 …”

“…For increasing PPS, introduction of a systemic therapy for patients in better condition with good hepatic function is an important issue, and possible with not only in cases with TKI but also Atez/Bev treatments. As noted in previous reports of mPFS and mOS in CP‐B patients treated with Atez/Bev, 36,37 the present results regarding PFS and OS indicate that the opportunity for migration to post‐progression treatment as well as clinical benefits from sequential post‐progression therapy are reduced in patients with CP‐B as compared to those with CP‐A.…”

“…Atez/Bev is a newly developed treatment method, though the prognosis of patients when divided by hepatic function grade (i.e., Child-Pugh score 22 or mALBI grade 23 ) has not been adequately elucidated. (mPFS/mOS = 2.9/6.0 months, n = 37) 36 and D'Alessio (mPFS/ mOS = 2.3/6.5 months, n = 18). 37 Generally, good hepatic function (CP-A) is considered to be required for introducing a therapeutic modality for systemic treatment in patients with u-HCC in order to obtain a good therapeutic response with good tolerability.…”

Outcome of patients with HCC and liver dysfunction under immunotherapy: a systematic review and meta-analysis

“…Thereafter, 21 articles were excluded and 15 studies were finally included for meta-analysis (1 clinical trial and 14 observational studies), [13,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] 4 of these being abstracts. [25][26][27][28] Between reviewer agreement for the inclusion process was 0.75 (95% CI, 0.70-0.80), as assessed by the kappa coefficient. There was disagreement with respect to 4 studies and it was resolved by a third reviewer (M.R.…”

“…[20][21][22] Regardless the lack of any evidence, it has been widely hypothesized that immunotherapy could potentially have a less pronounced impact on liver function and could be safer for HCC patients with liver dysfunction, resulting in improved survival. However, until now only 1 single-arm clinical trial with nivolumab in first-line or after sorafenib [12] has evaluated this population and some immunotherapy-based regimes [23][24][25][26][27][28][29][30][31][32][33][34][35][36] have assessed this special population and in real-life studies reported heterogeneous results.…”