Comparison of atezolizumab plus bevacizumab and lenvatinib in terms of efficacy and safety as primary systemic chemotherapy for hepatocellular carcinoma

Maesaka, Kazuki; Sakamori, Ryotaro; Yamada, Ryotaro; Doi, Akira; Tahata, Yuki; Miyazaki, Masao; Ohkawa, Kazuyoshi; Mita, Eiji; Iio, Sadaharu; Nozaki, Yuichi; Yakushijin, Takayuki; Imai, Yumiko; Kodama, Tatsuhiko; Tatsumi, Tomohide; Takehara, Tetsuo

doi:10.1111/hepr.13771

Cited by 38 publications

(70 citation statements)

References 25 publications

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“…Considering these points, it is reasonable to conclude that ATEZO/BEVA has a better prognosis than LEN. Moreover, the median observation period of ATEZO/BEVA treatment was longer than in previous studies [ 6 , 7 , 17 ], which we consider a more meaningful result. Additionally, a previous report clarified that the combination of ATEZO/BEVA is superior to LEN based on a matching-adjusted indirect comparison (MAIC) using data on LEN from patients outside of randomized trials, as well as data on the ATEZO/BEVA results derived from the IMbrave150 trial [ 18 ].…”

Section: Discussionmentioning

confidence: 65%

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Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

et al. 2022

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Background A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. Objective This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. Patients and Methods This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA ( n = 186) or LEN ( n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. Results After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). Conclusions ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-022-00921-x.

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Section: Discussionmentioning

confidence: 65%

“…No clinical trial has directly compared the therapeutic effects and safety between ATEZO/BEVA and LEN. Recently, although some retrospective analyses have compared ATEZO/BEVA and LEN for HCC patients [ 6 , 7 ], the efficacy and safety of ATEZO/BEVA and LEN remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

et al. 2022

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“…The combination of atezolizumab with bevacizumab is the first-line treatment, exhibiting a breakthrough ORR of 33.2% and median PFS of 6.8 months and proving the superiority compared to sorafenib in survival benefit ( 22 – 24 ). According to Maesaka et al., although the median PFS was significantly longer in the atezolizumab plus bevacizumab group (8.8 months vs. 5.2 months), there were no significant differences in terms of median OS (not reached vs. 20.6 months) or ORR (43.8% vs. 52.4%) ( 25 ). If lenvatinib plus TACE therapy can improve PFS, and achieve results matching the atezolizumab plus bevacizumab therapy requires further study.…”

Section: Introductionmentioning

confidence: 99%

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Sun

Xu²,

Meng

et al. 2022

Front. Oncol.

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Lenvatinib plus transarterial chemoembolization (TACE)have become the first choice for patients with hepatocellular carcinoma (HCC) that are unsuitable for TACE. Sorafenib plus TACE therapy for patients with portal vein tumor thrombus (PVTT) achieved positive results. However, Lenvatinib plus TACE appeared to achieve a more advantageous result for these patients based on the phase 3 REFLECT trial. Both TACE and lenvatinib therapy have immune-stimulating effects, so would lenvatinib plus TACE and immune checkpoint inhibitors be an advantageous therapy for unresectable HCC (uHCC)? Thirteen articles from PubMed were explored to determine the efficacy and safety of lenvatinib plus TACE with or without PD-1 inhibitors therapy. Most of the adverse events (AEs) were manageable. Lenvatinib plus TACE therapy was superior to lenvatinib monotherapy with intermediate stage HCC especially beyond up-to-seven criterion and was superior to TACE monotherapy in patients with uHCC or sorafenib plus TACE therapy in patients with PVTT. Objective response rates (ORRs) of 53.1%–75%, median progression free survival (PFS) of 6.15–11.6 months, and median overall survival (OS) of 14.5–18.97 months were achieved in the lenvatinib plus TACE group. Levatinib plus TACE and PD-1 inhibitors achieved ORRs of 46.7% –80.6%, median PFS of 7.3–13.3 months, and median OS of 16.9–24 months. Control studies also confirmed the triple therapy was superior to lenvatinib plus TACE in patients with uHCC. Overall, the triple therapy is a promising treatment for patients with uHCC, including main PVTT and extrahepatic metastasis. Lenvatinib plus TACE therapy was also preferable for intermediate stage HCC beyond up-to-seven criterion and for patients with PVTT.

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“…Two studies focused on the efficacy and safety of nivolumab, and the remaining one focused on pembrolizumab. A total of seven studies used combination therapy of ICIs and angiogenesis inhibitory monoclonal antibodies (AI mAbs) as the treatment of intervention group [13,[35][36][37][38][39][40]. Three studies examined atezolizumab plus bevacizumab, followed by sintilimab plus IBI305 (n = 1), toripalimab plus bevacizumab (n = 1), ezabenlimab plus BI 836,880 (n = 1), and durvalumab plus bevacizumab (n = 1).…”

Section: Study Drugsmentioning

confidence: 99%

Efficacy and safety of monotherapy and combination therapy of immune checkpoint inhibitors as first-line treatment for unresectable hepatocellular carcinoma: a systematic review, meta-analysis and network meta-analysis

et al. 2022

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Background Hepatocellular carcinoma (HCC) is one of the cancers with the highest morbidity and mortality. Sorafenib used to be the main treatment for unresectable HCC patients. However, regimens based on immune checkpoint inhibitors (ICIs) have attracted attention in recent years because of their reported benefits. This study aimed to evaluate the efficacy and safety of monotherapy and combination therapy of ICIs as first-line treatment for unresectable HCC patients by conducting a systematic review, meta-analysis, and network meta-analysis. Methods Studies published up to 11st August 2022 were searched from 4 commonly used databases, including PubMed, Web of Science, Embase, and Clinical trials.gov. All eligible clinical trials were included. Data about reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were extracted. Results Of the 8579 studies retrieved, 24 met the inclusion criteria. In patients with unresectable HCC taking ICIs-based therapy as first-line treatment, the pooled result of median PFS and median OS was 5.76 months (95% CI 4.82–6.69) and 16.35 months (95% CI 15.19–17.51) The ORR and DCR were 25.1% (95% CI 20.8–29.5%) and 75.2% (95% CI 70.3–80.2%) measured by RECIST v1.1 or 40.2% (95% CI 31.7–48.6%) with 75.2% (95% CI 68.3–82.1%) measured by mRECIST v1.1. Compared to sorafenib, ICIs-based therapy significantly prolonged OS. The combination treatment of sintilimab plus IBI305 had the highest ORR, while atezolizumab plus bevacizumab had the highest DCR. The pooled incidence of any grade TRAEs was 82.3% (95% CI 73.9–90.7%), with highest incidence appeared in dysphonia. Conclusions This study demonstrated that first-line ICIs-based therapies could provide survival benefits for patients with unresectable HCC, with manageable TRAEs. The potential of combination treatment to become the new treatment trend in clinical practice is promising.

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Comparison of atezolizumab plus bevacizumab and lenvatinib in terms of efficacy and safety as primary systemic chemotherapy for hepatocellular carcinoma

Cited by 38 publications

References 25 publications

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Efficacy and safety of monotherapy and combination therapy of immune checkpoint inhibitors as first-line treatment for unresectable hepatocellular carcinoma: a systematic review, meta-analysis and network meta-analysis

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