Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma: Early clinical experience

Hiraoka, Atsushi; Kumada, Takashi; Tada, Toshifumi; Hirooka, Masashi; Kariyama, Kazuya; Tani, Joji; Atsukawa, Masanori; Takaguchi, Koichi; Itobayashi, Ei; Fukunishi, Shinya; Tsuji, Kiichiro; Ishikawa, Toru; Tajiri, Kazuto; Ochi, Hironori; Yasuda, Satoshi; Toyoda, Hidenori; Ogawa, Chikara; Nishimura, Takashi; Hatanaka, Takeshi; Ohama, Hideko; Nouso, Kazuhiro; Morishita, Asahiro; Tsutsui, Akemi; Nagano, Takuya; Itokawa, Norio; Okubo, Tomomi; Arai, Taeang; Imai, Michitaka; Nakamura, Shinichiro; Joko, Kouji; Iijima, Hiroko; Hiasa, Yoichi; Kudo, Masatoshi

doi:10.1002/cnr2.1464

Cited by 50 publications

(62 citation statements)

References 45 publications

(67 reference statements)

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“…On the other hand, some reports on the initial experience of Atezo + Bev in real-world practice have already been reported. According to these reports, the efficacy was similar in patients who were initiated as first-line treatment and in patients who had a history of prior systemic treatment [14][15][16]. However, in our study, the ORR decreased slightly in the second-line or later treatment group, so this finding also needs further investigation.…”

Section: Discussionsupporting

confidence: 42%

Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice

Ando

Kawaoka

Kosaka

et al. 2021

Cancers

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The aim of this study was to investigate the early tumor response and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma in real-world practice. Forty patients with Child-Pugh class A liver function and eastern cooperative oncology group performance status 0 or 1 were enrolled. The objective response rate (ORR) at six weeks after the start of treatment, changes in α-fetoprotein (AFP) and des-γ-carboxyprothrombin, incidence of adverse events (AEs), and changes in albumin-bilirubin (ALBI) score and serum ammonia level, were evaluated. Among 40 patients, 24 had histories of prior molecular targeted agents (MTAs). The ORR was 22.5% based on mRECIST. Multivariate analysis showed that an AFP ratio <1.0 at three weeks (odds ratio 39.2, 95% confidence interval CI 2.37–649.0, p = 0.0103) was the only significant factor for predicting early response. There was no significant difference in the frequency of AEs between patients receiving first-line treatments and others. Fatigue, proteinuria, and ascites were more frequent in patients who experienced prior treatment. No decrease in ALBI score or increase in serum ammonia level was observed. Our study demonstrated that AFP may be useful in assessing early response and that this treatment is safe, including in patients with prior MTA treatments.

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Section: Discussionsupporting

confidence: 42%

Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice

Ando

Kawaoka

Kosaka

et al. 2021

Cancers

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“…Several real-world clinical studies have shown that Atezo/Bev therapy has comparable safety profiles and efficacy, as observed in the IMbrave150 study [4,5]. However, the objective response rate (ORR) and disease control rate (DCR) reported for Atezo/Bev in the updated analysis of the IMbrave150 trial are 29.8% and 73.9%, respectively [6].…”

Section: Introductionmentioning

confidence: 94%

Pretreatment Neutrophil-to-Lymphocyte Ratio as a Predictive Marker of Response to Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma

et al. 2021

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Background: Combination therapy with anti-programmed death-ligand 1 monoclonal antibody atezolizumab plus anti-vascular endothelial growth factor agent bevacizumab (Atezo/Bev) was approved in 2020 as a first-line treatment for unresectable hepatocellular carcinoma (HCC). Atezo/Bev therapy is relatively well tolerated; however, factors that can predict its response have not yet been reported. Thus, we aimed to investigate whether the pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict the therapeutic response in patients with HCC treated with Atezo/Bev therapy. Methods: We analyzed the course of 40 patients with HCC who received Atezo/Bev therapy at our hospital and attempted to identify pretreatment factors that could predict response by comparing those who achieved disease control with those who did not. Results: The pretreatment NLR value in patients who achieved disease control was significantly lower than that in patients with disease progression (2.47 vs. 4.48, p = 0.013). Using the optimal NLR cut-off value for predicting response (3.21) determined by receiver operating characteristic curve analysis, patients with NLR ≤ 3.21 had significantly better progression-free survival than those with NLR > 3.21 (p < 0.0001), although there were no significant differences in liver function or tumor-related background factors between the two groups. Conclusions: The pretreatment NLR value may be a useful predictor of response to Atezo/Bev therapy for HCC.

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“…10 The therapeutic potential of ATZ + BV for u-HCC in clinical practice has also been reported in several very recent studies. [11][12][13][14][15] However, since HCC patients with a history of MTA therapy and those with Child-Pugh B cirrhosis were excluded in the IMbrave150 trial, the recent reports about the safety and efficacy of ATZ + BV in these patients are not adequate. In real-world clinical practice, the combination therapy is used not only for MTA-naïve cases, but also as second-or third-line treatment in MTA-experienced cases.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, strictly speaking, there was a difference in the patient population between our study and Sho et al's report, which could have led to the observed difference in the therapeutic effect. Additionally, since some reports have shown that the effect of ATZ + BV does not differ depending on the patient's history of MTA,[11][12][13] while other reports have shown a difference,14,26,27 no consensus about this seems to have been reached as yet. Regarding the difference in treatment results of ATZ + BV as a later line therapy, it seems that the effect of ATZ + BV treatment also differs depending on whether the previous treatment was withdrawn due to AEs or PD.…”

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confidence: 99%

Safety and efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma in early clinical practice: A multicenter analysis

Chuma

Uojima

Hattori

et al. 2021

Hepatology Research

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Purpose: To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC).Method: Ninety-four u-HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B-IMbrave150-out group (n = 48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical characteristics, including neutrophil lymphocyte ratio (NLR) at baseline. Results:The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ + BV treatment due to fatigue was higher in CP-B than CP-A patients (p = 0.030). Objective response (OR) rates of the B-IMbrave150-in group (28.3%, 39.1%) were significantly higher than those of the B-IMbrave150-out group (8.3%, 18.8%; p = 0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, NLR (hazard ratio (HR), 4.591; p = 0.0160) and B-IMbrave150 criteria (HR,

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Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma: Early clinical experience

Abstract: Background: Although atezolizumab plus bevacizumab (Atez/bev) treatment has been developed for unresectable hepatocellular carcinoma (u-HCC), changes in hepatic function during therapy have yet to be reported.

Cited by 50 publications

References 45 publications

Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice

Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice

Pretreatment Neutrophil-to-Lymphocyte Ratio as a Predictive Marker of Response to Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma

Safety and efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma in early clinical practice: A multicenter analysis

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