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Erschienen in: Drugs 12/2023

04.07.2023 | Review Article

New Opportunities to Individualize Frontline Therapy in Advanced Stages of Hepatocellular Carcinoma

verfasst von: John D. Gordan, Bridget P. Keenan, Huat Chye Lim, Mark Yarchoan, R. Katie Kelley

Erschienen in: Drugs | Ausgabe 12/2023

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Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally and is rising in incidence. Until recently, treatment options for patients with advanced stages of HCC have been limited to antiangiogenic therapies with modest improvements in overall survival. The emerging role of immunotherapy with immune checkpoint inhibitors (ICI) in oncology has led to a rapid expansion in treatment options and improvements in outcomes for patients with advanced stages of HCC. Recent clinical trials have shown meaningful survival improvement in patients treated with the combination of bevacizumab and atezolizumab, as well as with the combination of tremelimumab with durvalumab, resulting in regulatory approvals of these regimens as frontline therapy. Beyond improvements in overall survival, ICI-based combination regimens achieve higher rates of durable treatment response than multikinase inhibitors and have favorable side effect profiles. With the emergence of doublet anti-angiogenic and immune checkpoint inhibitor (ICI) and dual ICI combinations, individualized therapy is now possible for patients based on co-morbidity profiles and other factors. These more potent systemic therapies are also being tested in earlier stages of disease and in combination with loco-regional therapies such as trans-arterial chemoembolization and stereotactic body radiotherapy. We summarize these advances and emerging therapeutic combinations currently in clinical trials.
Literatur
2.
Zurück zum Zitat Llovet JM, Hilgard P, de Oliveira AC, Forner A, Zeuzem S, Galle PR, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008. Llovet JM, Hilgard P, de Oliveira AC, Forner A, Zeuzem S, Galle PR, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008.
6.
9.
Zurück zum Zitat Global Burden of Disease Liver Cancer C, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3(12):1683–91. https://doi.org/10.1001/jamaoncol.2017.3055. Global Burden of Disease Liver Cancer C, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3(12):1683–91. https://​doi.​org/​10.​1001/​jamaoncol.​2017.​3055.
21.
52.
Zurück zum Zitat D’Alessio A, Fulgenzi CAM, Nishida N, Schonlein M, von Felden J, Schulze K, et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: a real-world study. Hepatology. 2022;76(4):1000-12. https://doi.org/10.1002/hep.32468. D’Alessio A, Fulgenzi CAM, Nishida N, Schonlein M, von Felden J, Schulze K, et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: a real-world study. Hepatology. 2022;76(4):1000-12. https://​doi.​org/​10.​1002/​hep.​32468.
53.
Zurück zum Zitat Tanaka T, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, et al. 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. Hepatol Res. 2022;52(9):773–83. https://doi.org/10.1111/hepr.13797.CrossRefPubMed Tanaka T, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, et al. 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. Hepatol Res. 2022;52(9):773–83. https://​doi.​org/​10.​1111/​hepr.​13797.CrossRefPubMed
56.
57.
59.
65.
Zurück zum Zitat Neely JY, Kudo M, et al., editor. Genomic and transcriptomic analyses related to the clinical efficacy of first-line nivolumab in advanced hepatocellular carcinoma from the phase 3 CheckMate 459 trial. New Orleans: American Association for Cancer Research; 2022. Neely JY, Kudo M, et al., editor. Genomic and transcriptomic analyses related to the clinical efficacy of first-line nivolumab in advanced hepatocellular carcinoma from the phase 3 CheckMate 459 trial. New Orleans: American Association for Cancer Research; 2022.
71.
Zurück zum Zitat Yasui Y, Tsuchiya K, Kurosaki M, Takeguchi T, Takeguchi Y, Okada M, et al. Up-to-seven criteria as a useful predictor for tumor downstaging to within Milan criteria and Child-Pugh grade deterioration after initial conventional transarterial chemoembolization. Hepatol Res. 2018;48(6):442–50. https://doi.org/10.1111/hepr.13048.CrossRefPubMed Yasui Y, Tsuchiya K, Kurosaki M, Takeguchi T, Takeguchi Y, Okada M, et al. Up-to-seven criteria as a useful predictor for tumor downstaging to within Milan criteria and Child-Pugh grade deterioration after initial conventional transarterial chemoembolization. Hepatol Res. 2018;48(6):442–50. https://​doi.​org/​10.​1111/​hepr.​13048.CrossRefPubMed
78.
Zurück zum Zitat Chen M, Chow PKH, Kaseb AO, Lee HC, Yopp AC, Becker L, et al. Efficacy, safety and patient reported outcomes (PROs) from the phase III IMbrave050 trial of adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation. J Clin Oncol. 2023;41(16_suppl):4002. https://doi.org/10.1200/JCO.2023.41.16_suppl.4002.CrossRef Chen M, Chow PKH, Kaseb AO, Lee HC, Yopp AC, Becker L, et al. Efficacy, safety and patient reported outcomes (PROs) from the phase III IMbrave050 trial of adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation. J Clin Oncol. 2023;41(16_suppl):4002. https://​doi.​org/​10.​1200/​JCO.​2023.​41.​16_​suppl.​4002.CrossRef
85.
Zurück zum Zitat Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y, et al. IMbrave150: updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC). J Clin Oncol. 2021;39(3_suppl):267. https://doi.org/10.1200/JCO.2021.39.3_suppl.267.CrossRef Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y, et al. IMbrave150: updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC). J Clin Oncol. 2021;39(3_suppl):267. https://​doi.​org/​10.​1200/​JCO.​2021.​39.​3_​suppl.​267.CrossRef
88.
Zurück zum Zitat Finn RSKM, Merle P et al., editor. Primary results from the phase 3 LEAP-002 study: lenvatinib plus pembrolizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma. Paris: 2022 European Society of Medical Oncology; 2022. Finn RSKM, Merle P et al., editor. Primary results from the phase 3 LEAP-002 study: lenvatinib plus pembrolizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma. Paris: 2022 European Society of Medical Oncology; 2022.
92.
Zurück zum Zitat Ryoo B-Y, Hsu C-H, Li D, Burgoyne A, Cotter C, Badhrinarayanan S, et al. Results from the MORPHEUS-liver study: phase Ib/II randomized evaluation of tiragolumab (tira) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC). J Clin Oncol. 2023;41(16_suppl):4010. https://doi.org/10.1200/JCO.2023.41.16_suppl.4010.CrossRef Ryoo B-Y, Hsu C-H, Li D, Burgoyne A, Cotter C, Badhrinarayanan S, et al. Results from the MORPHEUS-liver study: phase Ib/II randomized evaluation of tiragolumab (tira) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC). J Clin Oncol. 2023;41(16_suppl):4010. https://​doi.​org/​10.​1200/​JCO.​2023.​41.​16_​suppl.​4010.CrossRef
93.
Zurück zum Zitat Kelley RK, Cheng A-L, Kaseb A, Qin S, Zhu AX, Chan S, Sukeepaisarnjaroen W, Breder V, Verset G, Gane E, Borbath I, Gomez Rangel JD, Merle P, Benzaghou FM, Banerjee K, Hazra S, Fawcett J, Rimassa L. VP10-2021: cabozantinib (C) plus atezolizumab (A) versus sorafenib (S) as first-line systemic treatment for advanced hepatocellular carcinoma (aHCC): results from the randomized phase III COSMIC-312 trial. Ann Oncol. 2021. https://doi.org/10.1016/j.annonc.2021.10.008.CrossRef Kelley RK, Cheng A-L, Kaseb A, Qin S, Zhu AX, Chan S, Sukeepaisarnjaroen W, Breder V, Verset G, Gane E, Borbath I, Gomez Rangel JD, Merle P, Benzaghou FM, Banerjee K, Hazra S, Fawcett J, Rimassa L. VP10-2021: cabozantinib (C) plus atezolizumab (A) versus sorafenib (S) as first-line systemic treatment for advanced hepatocellular carcinoma (aHCC): results from the randomized phase III COSMIC-312 trial. Ann Oncol. 2021. https://​doi.​org/​10.​1016/​j.​annonc.​2021.​10.​008.CrossRef
109.
Zurück zum Zitat Meyer TMA, Borad MJ, Edeline J, Hausner PF, Hollebecque A, Goyal L, Evans J, Wong KM, Tan BR, Mitry E, Sarker D, Finn R, El-Khoueiry A, Feun LG, El-Rayes B, Thistlethwaite F, Kaseb A, Cirillo C, Noto P, Cristiani S, Sun A, Bruix J, Sangro B, editor. Overall safety and efficacy from the phase 1 trial of ADP-A2AFP SPEAR T-cells in patients with advanced hepatocellular carcinoma or other cancer types expressing alpha-fetoprotein. In: ILCA 16th annual conference; 2022 1–4 September 2022; Madrid, Spain. Meyer TMA, Borad MJ, Edeline J, Hausner PF, Hollebecque A, Goyal L, Evans J, Wong KM, Tan BR, Mitry E, Sarker D, Finn R, El-Khoueiry A, Feun LG, El-Rayes B, Thistlethwaite F, Kaseb A, Cirillo C, Noto P, Cristiani S, Sun A, Bruix J, Sangro B, editor. Overall safety and efficacy from the phase 1 trial of ADP-A2AFP SPEAR T-cells in patients with advanced hepatocellular carcinoma or other cancer types expressing alpha-fetoprotein. In: ILCA 16th annual conference; 2022 1–4 September 2022; Madrid, Spain.
Metadaten
Titel
New Opportunities to Individualize Frontline Therapy in Advanced Stages of Hepatocellular Carcinoma
verfasst von
John D. Gordan
Bridget P. Keenan
Huat Chye Lim
Mark Yarchoan
R. Katie Kelley
Publikationsdatum
04.07.2023
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 12/2023
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-023-01907-3

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