Skip to main content
Erschienen in: Im Fokus Onkologie 4/2022

31.08.2022 | Hepatozelluläres Karzinom | Gastroonkologie

Fortschritte in der Therapie des hepatozellulären Karzinoms

Von der zielgerichteten zur immunonkologischen Systemtherapie

verfasst von: Prof. Dr. med. Arndt Vogel, Dr. med. Christoph Gerdes

Erschienen in: Im Fokus Onkologie | Ausgabe 4/2022

Einloggen, um Zugang zu erhalten

Auszug

Das hepatozelluläre Karzinom (HCC) ist eines der häufigsten Tumoren weltweit und weist eine hohe Mortalität auf. Verschiedene Therapieoptionen stehen mit Chirurgie, lokalablativen Verfahren, Strahlentherapie und Systemtherapien zur Verfügung. Dies erfordert ein multidisziplinäres Team, welches individuell anhand des Tumorstadiums, der Leberfunktion und des physischen Zustands die Behandlung der Patientinnen und Patienten festlegt. Insbesondere die Systemtherapien haben in den letzten Jahren einen durchgreifenden Wandel erfahren, sodass sich unter anderem mit den Immuntherapien neue Möglichkeiten, aber auch Herausforderungen ergeben.
Literatur
1.
Zurück zum Zitat Sung H et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):20949 Sung H et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):20949
2.
Zurück zum Zitat Reig M et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681-93 Reig M et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681-93
3.
Zurück zum Zitat Azoulay D et al. Liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension. JHEP Rep. 2020;3(1):100190 Azoulay D et al. Liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension. JHEP Rep. 2020;3(1):100190
5.
Zurück zum Zitat Zhu AX et al. Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab. Br J Cancer. 2021;124(8):1388-97 Zhu AX et al. Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab. Br J Cancer. 2021;124(8):1388-97
6.
Zurück zum Zitat Vogel A et al. Baseline Liver Function and Subsequent Outcomes in the Phase 3 REFLECT Study of Patients with Unresectable Hepatocellular Carcinoma. Liver Cancer. 2021;10(5):510-21 Vogel A et al. Baseline Liver Function and Subsequent Outcomes in the Phase 3 REFLECT Study of Patients with Unresectable Hepatocellular Carcinoma. Liver Cancer. 2021;10(5):510-21
7.
Zurück zum Zitat Vogel A et al. ALBI score and outcomes in patients with hepatocellular carcinoma: post hoc analysis of the randomized controlled trial KEYNOTE-240.Ther Adv Med Oncol. 2021;13:17588359211039928. Vogel A et al. ALBI score and outcomes in patients with hepatocellular carcinoma: post hoc analysis of the randomized controlled trial KEYNOTE-240.Ther Adv Med Oncol. 2021;13:17588359211039928.
8.
Zurück zum Zitat Kudo M et al. Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2. JHEP Rep. 2020;3(2):100215 Kudo M et al. Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2. JHEP Rep. 2020;3(2):100215
9.
Zurück zum Zitat Johnson PJ et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550-8 Johnson PJ et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550-8
10.
Zurück zum Zitat Bruix J et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015;16(13):1344-54 Bruix J et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015;16(13):1344-54
11.
Zurück zum Zitat Ho WJ et al. Neoadjuvant Cabozantinib and Nivolumab Converts Locally Advanced HCC into Resectable Disease with Enhanced Antitumor Immunity. Nat Cancer. 2021;2(9):891-903 Ho WJ et al. Neoadjuvant Cabozantinib and Nivolumab Converts Locally Advanced HCC into Resectable Disease with Enhanced Antitumor Immunity. Nat Cancer. 2021;2(9):891-903
12.
Zurück zum Zitat Kaseb AO et al. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022;7(3):208-18 Kaseb AO et al. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022;7(3):208-18
13.
Zurück zum Zitat Marron TU et al. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022;7(3):219-29 Marron TU et al. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022;7(3):219-29
14.
Zurück zum Zitat Llovet JM et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-90 nach 13. Cheng AL et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25-34 Llovet JM et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-90 nach 13. Cheng AL et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25-34
16.
Zurück zum Zitat McNamara MG, Slagter AE, Nuttall C, et al. Sorafenib as first-line therapy in patients with advanced Child-Pugh B hepatocellular carcinoma-a meta-analysis. Eur J Cancer. 2018;105:1-9 McNamara MG, Slagter AE, Nuttall C, et al. Sorafenib as first-line therapy in patients with advanced Child-Pugh B hepatocellular carcinoma-a meta-analysis. Eur J Cancer. 2018;105:1-9
17.
Zurück zum Zitat Meyer T et al. Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2017;2(8):565-75 nach 16. Kudo M et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-73 Meyer T et al. Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2017;2(8):565-75 nach 16. Kudo M et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-73
18.
Zurück zum Zitat Alsina A et al. Effects of Subsequent Systemic Anticancer Medication Following First-Line Lenvatinib: A Post Hoc Responder Analysis from the Phase 3 REFLECT Study in Unresectable Hepatocellular Carcinoma. Liver Cancer. 2020;9(1):93-104 Alsina A et al. Effects of Subsequent Systemic Anticancer Medication Following First-Line Lenvatinib: A Post Hoc Responder Analysis from the Phase 3 REFLECT Study in Unresectable Hepatocellular Carcinoma. Liver Cancer. 2020;9(1):93-104
19.
Zurück zum Zitat Vogel A et al. Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2021;6(8):649-65 Vogel A et al. Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2021;6(8):649-65
20.
Zurück zum Zitat Welland S et al. Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A Retrospective Multicenter Study. Liver Cancer. 2022 Feb 10;11(3):219-32 Welland S et al. Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A Retrospective Multicenter Study. Liver Cancer. 2022 Feb 10;11(3):219-32
21.
Zurück zum Zitat Bruix J et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2017 Jan 7;389(10064):36]. Lancet. 2017;389(10064):56-66 Bruix J et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2017 Jan 7;389(10064):36]. Lancet. 2017;389(10064):56-66
22.
Zurück zum Zitat Finn RS et al. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial. J Hepatol. 2018;69(2):353-58 Finn RS et al. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial. J Hepatol. 2018;69(2):353-58
23.
Zurück zum Zitat Teufel M et al. Biomarkers Associated With Response to Regorafenib in Patients With Hepatocellular Carcinoma. Gastroenterology. 2019;156(6):1731-41 Teufel M et al. Biomarkers Associated With Response to Regorafenib in Patients With Hepatocellular Carcinoma. Gastroenterology. 2019;156(6):1731-41
24.
Zurück zum Zitat Abou-Alfa GK et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018;379(1):54-63 Abou-Alfa GK et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018;379(1):54-63
25.
Zurück zum Zitat Zhu AXet al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015;16(7):859-70 Zhu AXet al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015;16(7):859-70
26.
Zurück zum Zitat Zhu AX et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-96 Zhu AX et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-96
27.
Zurück zum Zitat Zhu AX et al. Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: patient-reported outcomes across two randomised clinical trials. ESMO Open. 2020;5(4):e000797. doi:10.1136/esmoopen-2020-000797 Zhu AX et al. Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: patient-reported outcomes across two randomised clinical trials. ESMO Open. 2020;5(4):e000797. doi:10.1136/esmoopen-2020-000797
28.
Zurück zum Zitat Finn RS et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894-905 Finn RS et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894-905
29.
Zurück zum Zitat Cheng AL et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76(4):862-73 Cheng AL et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76(4):862-73
30.
Zurück zum Zitat Galle PR et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(7):991-1001 Galle PR et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(7):991-1001
31.
Zurück zum Zitat de Castro T et al. Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience. Ther Adv Med Oncol. 2022;14:17588359221080298 de Castro T et al. Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience. Ther Adv Med Oncol. 2022;14:17588359221080298
33.
Zurück zum Zitat Kelley RK et al. Cabozantinib in combination with atezolizumab versus sorafenib in treatment-naive advanced hepatocellular carcinoma: COSMIC-312 Phase III study design. Future Oncol. 2020;16(21):1525-36 Kelley RK et al. Cabozantinib in combination with atezolizumab versus sorafenib in treatment-naive advanced hepatocellular carcinoma: COSMIC-312 Phase III study design. Future Oncol. 2020;16(21):1525-36
34.
Zurück zum Zitat El-Khoueiry AB et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492-502 oder??? Yau T, Kang YK, Kim TY, et al. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial JAMA Oncol. 2020;6(11):e204564. El-Khoueiry AB et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492-502 oder??? Yau T, Kang YK, Kim TY, et al. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial JAMA Oncol. 2020;6(11):e204564.
35.
Zurück zum Zitat Yau T et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23(1):77-90 Yau T et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23(1):77-90
36.
Zurück zum Zitat Finn RS et al. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020;38(3):193-202 Finn RS et al. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020;38(3):193-202
Metadaten
Titel
Fortschritte in der Therapie des hepatozellulären Karzinoms
Von der zielgerichteten zur immunonkologischen Systemtherapie
verfasst von
Prof. Dr. med. Arndt Vogel
Dr. med. Christoph Gerdes
Publikationsdatum
31.08.2022
Verlag
Springer Medizin
Erschienen in
Im Fokus Onkologie / Ausgabe 4/2022
Print ISSN: 1435-7402
Elektronische ISSN: 2192-5674
DOI
https://doi.org/10.1007/s15015-022-3910-3

Weitere Artikel der Ausgabe 4/2022

Im Fokus Onkologie 4/2022 Zur Ausgabe

Passend zum Thema

ANZEIGE

Magenkarzinom: Experten geben Handlungsempfehlungen

Die Sequenztherapie beim metastasierten Adenokarzinom des Magens und des gastroösophagealen Übergangs (AEG) spielt eine immer größere Rolle. Speziell für die ideale Integration einer Taxan-haltigen Behandlung im Therapiealgorithmus stellen sich Fragen: Ein Expertenkonsens gibt konkrete Handlungsempfehlungen für den Praxisalltag.

ANZEIGE

Zwischen Trend & Kausalität: Kaffee & Überleben

4 und mehr Tassen Kaffee am Tag können das Sterberisiko bei Patienten mit mCRC um 36 % senken – verglichen mit Kaffee-Abstinenzlern. Dies und Weiteres deutet eine kürzlich in JAMA veröffentlichte Studie an. Was bringt Kaffee bei Darmkrebs und wie macht er das?

ANZEIGE

GI-Tumore und die Rolle von Angiogenesehemmern

Entdecken Sie mit praxisrelevanten Patientenfällen, kompakten Studieninhalten, informativen Experteninterviews und weiteren spannenden Inhalten, wie Sie den vielseitigen Herausforderungen bei GI-Tumoren begegnen können. Hier erfahren Sie mehr!