Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

Rimini, Margherita; Rimassa, Lorenza; Ueshima, Kazuomi; Burgio, Valentina; Shigeo, S.; Tada, Toshifumi; Suda, Goki; Yoo, Chang Young; Cheon, Jaekyung; Pinato, David J.; Lonardi, Sara; Scartozzi, Mario; Iavarone, M.; Costanzo, Giovan Giuseppe Di; Marra, Fabio; Soldà, Caterina; Tamburini, Emiliano; Piscaglia, Fabio; Masi, Gianluca; Cabibbo, Giuseppe; Foschi, Francesco Giuseppe; Silletta, Marianna; Pressiani, Tiziana; Nishida, Naoshi; Iwamoto, Hideki; Sakamoto, Naoya; Ryoo, Baek‐Yeol; Chon, Hong Jae; Claudia, Forlani; Nishizaki, Takashi; Sho, Takuya; Kang, Beodeul; D’Alessio, Antonio; Kumada, Takashi; Hiraoka, Atsushi; 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; Nishimur, T.; Hatanaka, Takeshi; Kakizaki, Satoru; Shimada, Noritomo; Kawata, Kazuhito; Tanaka, Takaaki; Ohama, Hideko; Nouso, Kazuhiro; Morishita, Asahiro; Tsutsui, Akemi; Nagano, Takuya; Itokawa, Norio; Okubo, Tomomi; Arai, Taeang; Imai, Michitaka; Naganuma, Akira; Koizumi, Yohei; Nakamura, Shinichiro; Joko, Kouji; Iijima, Hiroko; Hiasa, Yoichi; Pedica, Federica; Cobelli, Francesco De; Ratti, Francesca; Alrighetti, L.; Kudo, Masatoshi; Cascinu, Stefano; Casadei‐Gardini, Andrea

doi:10.1016/j.esmoop.2022.100591

Cited by 84 publications

(88 citation statements)

References 53 publications

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“…Moreover, a separate metanalysis of five trials (REACH, REACH-2, METIV-HCC, CELESTIAL, and JET-HCC for a total of 2083 patients) did not show an impact of etiology on outcome of TKIs/anti-VEGF, as no differences in efficacy were found between the viral and non-viral HCCs ( p = 0.88) [ 60 ]. Results similar to those of meta-analyses have been found in a large retrospective study including almost 1000 patients with non-viral HCC in whom, after propensity score matching, lenvatinib provided a greater benefit in OS and PFS than atezo+beva [ 72 ].…”

Section: Biomarkers Of Response And/or Resistance To Immune Checkpoin...supporting

confidence: 73%

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Strategies and Biomarkers Predicting Response and/or Resistance

2023

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In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with hepatocellular carcinoma (HCC). Following the positive results of the IMbrave150 trial, the combination of atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) became the standard of care frontline treatment for patients with advanced stage HCC. Several other trials evaluated immunotherapy in HCC, demonstrating that ICIs-based regimens are currently the most effective treatment strategies and expanding the therapeutic possibilities. Despite the unprecedent rates of objective tumor response, not all patients benefit from treatment with ICIs. Therefore, in order to select the appropriate therapy as well as to correctly allocate medical resources and avoid unnecessary treatment-related toxicities, there is great interest in identifying the predictive biomarkers of response or resistance to immunotherapy-based regimens. Immune classes of HCC, genomic signatures, anti-drug antibodies, and patient-related factors (e.g., etiology of liver disease, gut microbiota diversity) have been associated to the response to ICIs, but none of the proposed biomarkers have been translated into clinical practice so far. Considering the crucial importance of this topic, in this review we aim to summarize the available data on tumor and clinical features associated with the response or resistance of HCC to immunotherapies.

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Section: Biomarkers Of Response And/or Resistance To Immune Checkpoin...supporting

confidence: 73%

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Strategies and Biomarkers Predicting Response and/or Resistance

2023

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“…In 2021, atezolizumab plus bevacizumab treatment was recommended as the first-line treatment for unresectable HCC, due to the superior survival to sorafenib [ 46 ]. However, the recently published results of a multicenter study showed that the treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab [ 47 ]. Meanwhile, the efficacy of anti-PD1 therapy in a phase III randomized trial of patients with advanced HCC has not shown statistically significant improvement due to drug resistance in some patients [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Wang

et al. 2022

Cancers

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Lenvatinib was approved in 2018 as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). This systematic review and meta-analysis aimed to provide the most updated evidence about the efficacy and safety of lenvatinib as a first-line treatment for unresectable HCC. An electronic search of the PubMed database, Web of Science, Embase, and Cochrane Library was undertaken to identify all relevant studies up to May 2022. The pooled effect sizes were calculated based on the random-effects model. One phase III randomized controlled trial and 23 retrospective studies of 2438 patients were eligible for analysis. For patients treated with lenvatinib as first-line treatment, the pooled median overall survival (OS), median progression-free survival (PFS), 1-year OS rate, 1-year PFS rate, objective response rate (ORR), and disease control rate (DCR) were 11.36 months, 6.68 months, 56.0%, 27.0%, 36.0% and 75.0%, respectively. Lenvatinib showed a significantly superior efficacy compared with sorafenib (HR for OS, 0.85 and HR for PFS, 0.72; OR for ORR, 4.25 and OR for DCR, 2.23). The current study demonstrates that lenvatinib can provide better tumor responses and survival benefits than sorafenib as a first-line treatment for unresectable HCC, with a comparable incidence of adverse events.

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“…Further studies are needed to optimize sequential systemic drug therapy for lenvatinib-refractory HCC. Furthermore, combining lenvatinib with TACE to enhance antitumor effects (50) has a significant survival benefit, particularly in patients with non-viral HCC (51). Additionally, in the final analysis for the phase II trial (TACTICS-L trial), the combination of TACE and lenvatinib showed promising therapeutic efficacy in patients with unresectable HCC (52).…”

Section: B-5 Systemic Therapiesmentioning

confidence: 99%

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Japanese perspective

Koga¹,

Iwamoto²,

Suzuki³

et al. 2023

Clin Mol Hepatol

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Striking advances in systemic therapy for unresectable advanced hepatocellular carcinoma (HCC) have improved the average prognosis of patients with HCC. As a result, the guidelines for the treatment of HCC have changed significantly. However, various issues have emerged in clinical practice. First, there is no established biomarker that can predict response to systemic therapy. Second, there is no established treatment regimen after primary systemic therapy, including combined immunotherapy. Third, there is no established treatment regimen for intermediate-stage HCC. These points make the current guidelines ambiguous. In this review, we present the Japanese guidelines for the diagnosis and treatment of HCC based on the latest evidence; introduce various efforts mainly in Japanese real-life practice to update these guidelines; and present our perspectives on future guidelines.

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Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

Cited by 84 publications

References 53 publications

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Strategies and Biomarkers Predicting Response and/or Resistance

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Strategies and Biomarkers Predicting Response and/or Resistance

Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Japanese perspective

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