Recent advances in the management of hepatocellular carcinoma
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Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function. These advances have led to improvement in survival outcomes, with expected survival of greater than 18 months, in those with sensitive tumors, adequate liver function, and those functionally fit to receive sequential therapies. Several ongoing and promising trials are now evaluating combinational strategies with novel systemic agents and combinations of systemic therapy with locoregional therapy. In view of these trials, further advances in the treatment of HCC are foreseen in the near future.
Abstract
Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function. These advances have led to improvement in survival outcomes, with expected survival of greater than 18 months, in those with sensitive tumors, adequate liver function, and those functionally fit to receive sequential therapies. Several ongoing and promising trials are now evaluating combinational strategies with novel systemic agents and combinations of systemic therapy with locoregional therapy. In view of these trials, further advances in the treatment of HCC are foreseen in the near future.
참고문헌 (68)
- Lee YT, "The mortality and overall survival trends of primary liver cancer in the United States", J Natl Cancer Inst, 113, pp.1531~1541 (2021)
- Yang JD, "A global view of hepatocellular carcinoma : trends, risk, prevention and management", Nat Rev Gastroenterol Hepatol, 16, pp.589~604 (2019)
- Llovet JM, "Hepatocellular carcinoma", Nat Rev Dis Primers, 7, pp.6~ (2021)
- Lee YT, "State-Level HCC incidence and association with obesity and physical activity in the United States", Hepatology, 74, pp.1384~1394 (2021)
- "CT/MRI LI-RADS® v2017 CORE"[URL]
- Yang JD, "New advances in the diagnosis and management of hepatocellular carcinoma", BMJ, 371, pp.m3544~ (2020)
- European Association for the Study of the Liver, "EASL Clinical Practice Guidelines : Management of hepatocellular carcinoma", J Hepatol, 69, pp.182~236 (2018)
- Llovet JM, "Prognosis of hepatocellular carcinoma : the BCLC staging classification", Semin Liver Dis, 19, pp.329~338 (1999)
- Marrero JA, "Diagnosis, staging, and management of hepatocellular carcinoma : 2018 Practice Guidance by the American Association for the Study of Liver Diseases", Hepatology, 68, pp.723~750 (2018)
- Llovet JM, "Natural history of untreated nonsurgical hepatocellular carcinoma : rationale for the design and evaluation of therapeutic trials", Hepatology, 29, pp.62~67 (1999)
- Llovet JM, "Sorafenib in advanced hepatocellular carcinoma", N Engl J Med, 359, pp.378~390 (2008)
- Kudo M, "Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma : a randomised phase 3non-inferiority trial", Lancet, 391, pp.1163~1173 (2018)
- Finn RS, "Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma", N Engl J Med, 382, pp.1894~1905 (2020)
- Abou-Alfa GK, "Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma", NEJM Evid, 1, pp.EVIDoa2100070~ (2022)
- Bruix J, "Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment(RESORCE) : a randomised, double-blind, placebo-controlled, phase 3 trial", Lancet, 389, pp.56~66 (2017)
- Abou-Alfa GK, "Cabozantinib in patients with advanced and progressing hepatocellular carcinoma", N Engl J Med, 379, pp.54~63 (2018)
- Zhu AX, "Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations(REACH-2) : a randomised, double-blind, placebocontrolled, phase 3 trial", Lancet Oncol, 20, pp.282~296 (2019)
- Sangro B, "A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C", J Hepatol, 59, pp.81~88 (2013)
- El-Khoueiry AB, "Nivolumab in patients with advanced hepatocellular carcinoma(CheckMate 040) : an open-label, non-comparative, phase 1", 2 dose escalation and expansion trial, 2017, pp.389, 2492~2502
- Zhu AX, "Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib(KEYNOTE-224) : a non-randomised, open-label phase 2 trial", Lancet Oncol, 19, pp.940~952 (2018)
- Yau T, "Nivolumab versus sorafenib in advanced hepatocellular carcinoma(CheckMate 459) : a randomised, multicentre, open-label, phase 3 trial", Lancet Oncol, 23, pp.77~90 (2022)
- Finn RS, "Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240 : A randomized, double-blind, phase III trial", J Clin Oncol, 38, pp.193~202 (2020)
- Qin S, "Pembrolizumab versus placebo as second-line therapy in patients from Asia with advanced hepatocellular carcinoma : A randomized, double-blind, phase III trial", J Clin Oncol, 41, pp.1434~1443 (2023)
- Finn RS, "IMbrave150 : updated overall survival data from a global, randomized, open-label Phase III study of atezolizumab+ bevacizumab vs sorafenib in patients with unresectable hepatocellular carcinoma", J Clin Oncol, 39(3 suppl), pp.267~ (2021)
- Fulgenzi CAM, "Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice : Results of the AB-real study", Eur J Cancer, 175, pp.204~213 (2022)
- Yau T, "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, 6, pp.e204564~ (2020)
- Eisenhauer EA, "New response evaluation criteria in solid tumours : revised RECIST guideline(version 1. 1)", Eur J Cancer, 45, pp.228~247 (2009)
- Shigeta K, "Dual programmed death receptor-1 and vascular endothelial growth factor receptor-2 blockade promotes vascular normalization and enhances antitumor immune responses in hepatocellular carcinoma", Hepatology, 71, pp.1247~1261 (2020)
- Wallin JJ, "Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma", Nat Commun, 7, pp.12624~ (2016)
- Socinski MA, "Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC", N Engl J Med, 378, pp.2288~2301 (2018)
- Ziogas AC, "VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2", Int J Cancer, 130, pp.857~864 (2012)
- Motz GT, "The parallel lives of angiogenesis and immunosuppression : cancer and other tales", Nat Rev Immunol, 11, pp.702~711 (2011)
- Yang J, "Targeting VEGF", VEGFR to modulate antitumor immunity, 2018, pp.9, 978~
- Kandalaft LE, "Angiogenesis and the tumor vasculature as antitumor immune modulators : the role of vascular endothelial growth factor and endothelin", Curr Top Microbiol Immunol, 344, pp.129~148 (2011)
- Gabrilovich DI, "Coordinated regulation of myeloid cells by tumours", Nat Rev Immunol, 12, pp.253~268 (2012)
- Motz GT, "Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors", Nat Med, 20, pp.607~615 (2014)
- Finn RS, "LBA34Primary results from the phase III LEAP-002 study : Lenvatinib plus pembrolizumab versus lenvatinib as first-line(1L)therapy for advanced hepatocellular carcinoma(aHCC)", Ann Oncol, 33(Suppl 7), pp.S1401~ (2022)
- Kelley RK, "Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma(COSMIC-312) : a multicentre, openlabel, randomised, phase 3 trial", Lancet Oncol, 23, pp.995~1008 (2022)
- Ren Z, "Sintilimab plus a bevacizumab biosimilar(IBI305)versus sorafenib in unresectable hepatocellular carcinoma(ORIENT-32) : a randomised, openlabel, phase 2-3 study", Lancet Oncol, 22, pp.977~990 (2021)
- Qin S, "LBA35 Camrelizumab(C)plus rivoceranib(R)vs. sorafenib(S)as first-line therapy for unresectable hepatocellular carcinoma(uHCC) : A randomized, phase III trial", Ann Oncol, 33(Suppl 7), pp.S1401~S1402 (2022)
- Colton M, "Reprogramming the tumour microenvironment by radiotherapy : implications for radiotherapy and immunotherapy combinations", Radiat Oncol, 15, pp.254~ (2020)
- Yu J, "Liver metastasis restrains immunotherapy efficacy via macrophagemediated T cell elimination", Nat Med, 27, pp.152~164 (2021)
- Deng L, "Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice", J Clin Invest, 124, pp.687~695 (2014)
- Young KH, "Optimizing timing of immunotherapy improves control of tumors by hypofractionated radiation therapy", PLoS One, 11, pp.e0157164~ (2016)
- Wehrenberg-Klee E, "Y-90radioembolization combined with a PD-1 inhibitor for advanced hepatocellular carcinoma", Cardiovasc Intervent Radiol, 41, pp.1799~1802 (2018)
- Chiang CL, "Combined stereotactic body radiotherapy and checkpoint inhibition in unresectable hepatocellular carcinoma : A potential synergistic treatment strategy", Front Oncol, 9, pp.1157~ (2019)
- Chiang CL, "Combined stereotactic body radiotherapy and immunotherapy versus transarterial chemoembolization in locally advanced hepatocellular carcinoma : A propensity score matching analysis", Front Oncol, 11, pp.798832~ (2021)
- Juloori A, "Phase 1 randomized trial of stereotactic body radiation therapy followed by nivolumab plus ipilimumab or nivolumab alone in advanced", unresectable hepatocellular carcinoma, 2023, pp.115, 202~213
- Ali MY, "Activation of dendritic cells by local ablation of hepatocellular carcinoma", J Hepatol, 43, pp.817~822 (2005)
- Fei Q, "High-dimensional single-cell analysis delineates radiofrequency ablation induced immune microenvironmental remodeling in pancreatic cancer", Cell Death Dis, 11, pp.589~ (2020)
- Wu H, "Palliative radiofrequency ablation accelerates the residual tumor progression through increasing tumor-infiltrating MDSCs and reducing T-Cell-mediated anti-tumor immune responses in animal model", Front Oncol, 10, pp.1308~ (2020)
- Shi L, "PD-1 blockade boosts radiofrequency ablation-elicited adaptive immune responses against tumor", Clin Cancer Res, 22, pp.1173~1184 (2016)
- Duffy AG, "Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma", J Hepatol, 66, pp.545~551 (2017)
- Zhang JX, "Safety and efficacy of transarterial chemoembolization and immune checkpoint inhibition with camrelizumab for treatment of unresectable hepatocellular carcinoma", J Hepatocell Carcinoma, 9, pp.265~272 (2022)
- Chew V, "Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma", Gut, 68, pp.335~346 (2019)
- Iyer RV, "A phase II study of atezolizumab(ATEZO)and bevacizumab(BEV)in combination with Y90 TARE in patients(pts)with hepatocellular carcinoma(HCC) : Y90+", -BEAT, 2023, pp.41(4 Suppl), TPS629~
- Peng Z, "Lenvatinib combined with transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma : A phase III, randomized clinical trial(LAUNCH)", J Clin Oncol, 41, pp.117~127 (2023)
- Öcal O, "Addition of Y-90 radioembolization increases tumor response and local disease control in hepatocellular carcinoma patients receiving sorafenib", Eur J Nucl Med Mol Imaging, 49, pp.4716~4726 (2022)
- Kudo M, "Randomised, multicentre prospective trial of transarterial chemoembolisation(TACE)plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma : TACTICS trial", Gut, 69, pp.1492~1501 (2020)
- Ho WJ, "Neoadjuvant cabozantinib and nivolumab converts locally advanced HCC into resectable disease with enhanced antitumor immunity", Nat Cancer, 2, pp.891~903 (2021)
- Zhu A, "Abstract CT284 : Phase 3 KEYNOTE-937 : Adjuvant pembrolizumab versus placebo in patients with hepatocellular carcinoma and complete radiologic response after surgical resection or local ablation", Cancer Res, 80(16 Suppl), pp.CT284~ (2020)
- Exposito MJ, "CA209-9DX: phase III, randomized, double-blind study of adjuvant nivolumab vs placebo for patients with hepatocellular carcinoma (HCC) at high risk of recurrence after curative resection or ablation", Ann Oncol, 29, pp.viii267~viii268 (2018)
- Hack SP, "IMbrave 050 : a Phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation", Future Oncol, 16, pp.975~989 (2020)
- Chow P, "Abstract CT003 : IMbrave050 : Phase 3 study of adjuvant atezolizumab+bevacizumab versus active surveillance in patients with hepatocellular carcinoma(HCC)at high risk of disease recurrence following resection or ablation", Cancer Res, 83(8_Suppl), pp.CT003~ (2023)
- Franses JW, "Neoadjuvant approaches in hepatocellular carcinoma : There’s no time like the present", Clin Cancer Res, 28, pp.2738~2743 (2022)
- D’Alessio A, "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, 76, pp.1000~1012 (2022)
- Iavarone M, "Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation", Am J Transplant, 19, pp.3176~3184 (2019)
- DeLeon TT, "Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation : the Mayo Clinic experience", J Gastrointest Oncol, 9, pp.1054~1062 (2018)
