Early response and safety of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in patients who do not meet IMbrave150 eligibility criteria

Sho, Takuya; Suda, Goki; Ogawa, Koji; Kimura, Megumi; Kubo, Akinori; Kitagataya, Takashi; Maehara, Osamu; Ohnishi, Shunsuke; Shigesawa, Taku; Nakamura, Akihisa; Yamada, Ryoichi; Ohara, Masatsugu; Kawagishi, Naoki; Natsuizaka, Mitsuteru; Nakai, Masato; Morikawa, Kenichi; Furuya, Ken; Baba, Masaru; Yamamoto, Yoshiya; Suzuki, Kazuharu; Izumi, Tohru; Meguro, Takeshi; Terashita, Katsumi; Ito, Jun; Miyagishima, Takuto; Sakamoto, Naoya

doi:10.1111/hepr.13693

Cited by 25 publications

(19 citation statements)

References 34 publications

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“…They showed good safety and efficacy for these patients. Interestingly, none of the 15 patients with hepatitis B experienced progressive disease [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers

Himmelsbach

Pinter

Scheiner

et al. 2022

Cancers

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The combination of atezolizumab and bevacizumab (A + B) is the new standard of care for the systemic first-line treatment of hepatocellular carcinoma (HCC). However, up to now there are only few data on the safety and efficacy of A + B in real life. We included patients with advanced HCC treated with A + B as first-line therapy at four cancer centers in Germany and Austria between December 2018 and August 2021. Demographics, overall survival (OS), and adverse events were assessed until 15 September 2021. We included 66 patients. Most patients had compensated cirrhosis (n = 34; 52%), while Child–Pugh class B cirrhosis was observed in 23 patients (35%), and class C cirrhosis in 5 patients (8%). The best responses included a complete response (CR) in 7 patients (11%), a partial response (PR) in 12 patients (18%), stable disease (SD) in 22 patients (33%), and progressive disease in 11 patients (17%). The median progression-free (PFS) survival was 6.5 months, while the median overall survival (OS) was not reached in this cohort (6-month OS: 69%, 12-month OS: 60%, 18-month OS: 58%). Patients with viral hepatitis seemed to have a better prognosis than patients with HCC of non-viral etiology. The real-world PFS and OS were comparable to those of the pivotal IMBRAVE trial, despite including patients with worse liver function in this study. We conclude that A + B is also highly effective in a real-life setting, with manageable toxicity, especially in patients with compensated liver disease. In patients with compromised liver function (Child B and C), the treatment showed low efficacy and, therefore, it should be well considered before administration to these patients.

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“…They showed good safety and efficacy for these patients. Interestingly, none of the 15 patients with hepatitis B experienced progressive disease [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers

Himmelsbach

Pinter

Scheiner

et al. 2022

Cancers

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“…Thus far, appropriate treatment for patients with unresectable HCC who fail to respond to lenvatinib has been an unmet clinical need. Thus, in addition to ICI therapy [ 33 ], TKIs with anti-EGF/EGFR, HGF/c-MET, and/or ANG-2/Tie-2 activity may be a potential therapeutic option. Further analysis is required to confirm this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Changes in Serum Growth Factors during Lenvatinib Predict the Post Progressive Survival in Patients with Unresectable Hepatocellular Carcinoma

Yang

Suda

Maehara

et al. 2022

Cancers

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Serum growth factor changes and their effect on prognosis during lenvatinib for unresectable hepatocellular carcinoma (HCC) remain underexplored. The sequential changes in serum growth factors during lenvatinib for unresectable HCC were evaluated in 58 patients using complete clinical data, and preserved serum was used to investigate changes in FGF-19, ANG-2, HGF, VEGF, and EGF. Patients with a complete response (CR), partial response (PR), and stable disease (SD) were evaluated for growth factor changes between the best response and progressive disease (PD) points, classified based on these changes, and evaluated by post progression survival (PPS). A total of 8, 24, 18, and 8 patients showed CR, PR, SD, and PD, respectively. Multivariate analysis revealed that age, relative dose intensity, and baseline ANG-2 were significantly associated with treatment response. Growth factor changes between the best response and PD points revealed that patients could be classified into four groups based on the EGF, ANG-2, and HGF changes. Although patient characteristics at baseline and PD, their response to lenvatinib, and PFS were similar among those groups, patients with an increase in all growth factors had significantly shorter PPS (median PPS was 553, 323, and 316 versus 173 days in groups 1–4 p = 0.032). We revealed that the evaluation of the changes in growth factors during lenvatinib could predict PPS.

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“…This study showed no significant difference between the pretreatment NLR and the therapeutic response. To understand the other factors associated with the therapeutic response, Sho et al reported that portal vein tumor thrombosis or the hepatitis B virus was significantly associated with PD ( p = 0.039, p = 0.050) [ 17 ]. However, in our study, it was unclear whether PD increased in the case of vascular infiltration because the number of patients with PD was small.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment Modified Albumin–Bilirubin Grade Is an Important Predictive Factor Associated with the Therapeutic Response and the Continuation of Atezolizumab plus Bevacizumab Combination Therapy for Patients with Unresectable Hepatocellular Carcinoma

et al. 2022

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Background: Atezolizumab plus bevacizumab (ATZ + BV) treatment is recommended as the first-line systemic therapy for patients with unresectable hepatocellular carcinoma (u-HCC). This study aimed to investigate the predictive factors of therapeutic response and the continuation of ATZ + BV treatment for u-HCC in a real-world setting. Methods: This retrospective study was conducted between January 2021 and April 2022. Twenty-eight patients with u-HCC, who were treated with ATZ + BV, were assessed for their treatment response, continuation, and adverse events (AEs). Results: Among the 28 patients, 24 were evaluated at the first imaging. The objective response rate (ORR) was 29.2% (n = 7), and 54.2% (n = 13) on the response evaluation criteria in solid tumors (RECIST 1.1) and in the modified RECIST (mRECIST) guidelines, respectively. Comparing the objective response (OR) group (n = 13) and the non-OR group (n = 11), the modified albumin–bilirubin (mALBI) grades 1 and 2a were found to be significant predictive factors for OR (p = 0.021) in the mRECIST guidelines. Among the 28 patients, 17 discontinued their treatment due to AEs. Comparing the treatment continuation (n = 11) and discontinuation groups (n = 17), a Child–Pugh score of five points (p = 0.009) and mALBI grades 1 and 2a (p = 0.020) were predictive factors with significant differences. Conclusions: Pretreatment mALBI grades 1 and 2a were the important predictive factors associated with the therapeutic response and the therapeutic continuation of ATZ + BV for patients with u-HCC.

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Early response and safety of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in patients who do not meet IMbrave150 eligibility criteria

Cited by 25 publications

References 34 publications

Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers

Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers

Changes in Serum Growth Factors during Lenvatinib Predict the Post Progressive Survival in Patients with Unresectable Hepatocellular Carcinoma

Pretreatment Modified Albumin–Bilirubin Grade Is an Important Predictive Factor Associated with the Therapeutic Response and the Continuation of Atezolizumab plus Bevacizumab Combination Therapy for Patients with Unresectable Hepatocellular Carcinoma

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