Analysis of targeted therapy combined with immunotherapy for hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Qianlin ,  LI Qiu

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

LI Qiu, Email: liqiu@scu.edu.cn

Keywords：

hepatocellular carcinoma; systemic therapy; immunotherapy; targeted therapy

DOI：

10.7507/1007-9424.202303055

Video：

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We briefly analyzed the research design and results through summarizing the latest hot spots relevant to targeted therapy in combination with immunotherapy (Abbreviated as “combination therapy” ) for hepatocellular carcinoma (HCC), aiming to provide references for clinical decision-making and future research directions. It was found that the clinical study results related to combination therapy for HCC were different by summarizing the study design and results of combination therapy for HCC in recent years, which might be closely related to the study design, drug selection, research objects selection, protocol implementation, and other factors. It is suggested that a variety of factors such as disease background should be considered when combination therapy for HCC is conducted in order to obtain a more comprehensive and objective understanding.

Citation： LIU Qianlin, LI Qiu. Analysis of targeted therapy combined with immunotherapy for hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(4): 392-396. doi: 10.7507/1007-9424.202303055 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin, 2020, 70(1): 7-30.
3.	Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 2008, 359(4): 378-390.
4.	Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017, 389(10064): 56-66.
5.	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. doi: 10.1001/jamaoncol.2020.4564.
6.	Kudo M, Finn RS, Edeline J, et al. Updated efficacy and safety of KEYNOTE-224: a phase Ⅱ study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Eur J Cancer, 2022, 167: 1-12.
7.	Yau T, Park JW, Finn RS, 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.
8.	Finn RS, Ryoo BY, Merle P, 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.
9.	Deeks ED. Cabozantinib: a review in advanced hepatocellular carcinoma. Target Oncol, 2019, 14(1): 107-113.
10.	Lee MS, Ryoo BY, Hsu CH, et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol, 2020, 21(6): 808-820.
11.	Finn RS, Qin S, Ikeda M, 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(suppl_3): 267.
12.	Ren Z, Xu J, Bai Y, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol, 2021, 22(7): 977-990.
13.	Akula SM, Abrams SL, Steelman LS, et al. RAS/RAF/MEK/ERK, PI3K/PTEN/AKT/mTORC1 and TP53 pathways and regulatory miRs as therapeutic targets in hepatocellular carcinoma. Expert Opin Ther Targets, 2019, 23(11): 915-929.
14.	Kelley RK, Rimassa L, Cheng AL, et al. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol, 2022, 23(8): 995-1008.
15.	Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med, 2018, 379(1): 54-63.
16.	Qin S, Chan LS, Gu S, et al. LBA35 camrelizumab (C) plus rivoceranib (R) versus sorafenib (S) as first-line therapy for unresectable hepatocellular carcinoma (uHCC): a randomized, phase Ⅲ trial. Ann Oncol, 2022, 33(suppl): 1401-1402.
17.	Finn R, Kudo M, Merle P, et al. Primary 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, 2022, 33(suppl_7): S808-S869.
18.	Zhang Y, Xu J, Shen J, et al. Update on overall survival (OS) of RESCUE: an open-label, phase 2 trial of camrelizumab (C) in combination with apatinib (A) in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol, 2021, 39(15_suppl): 4076. doi: 10.1200/JCO.2021.39.15_suppl.4076.
19.	Xu J, Shen J, Gu S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase Ⅱ trial. Clin Cancer Res, 2021, 27(4): 1003-1011.
20.	Finn RS, Ikeda M, Zhu AX, et al. Phase Ⅰb study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol, 2020, 38(26): 2960-2970.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin, 2020, 70(1): 7-30.
3. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 2008, 359(4): 378-390.
4. Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017, 389(10064): 56-66.
5. 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. doi: 10.1001/jamaoncol.2020.4564.
6. Kudo M, Finn RS, Edeline J, et al. Updated efficacy and safety of KEYNOTE-224: a phase Ⅱ study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Eur J Cancer, 2022, 167: 1-12.
7. Yau T, Park JW, Finn RS, 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.
8. Finn RS, Ryoo BY, Merle P, 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.
9. Deeks ED. Cabozantinib: a review in advanced hepatocellular carcinoma. Target Oncol, 2019, 14(1): 107-113.
10. Lee MS, Ryoo BY, Hsu CH, et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol, 2020, 21(6): 808-820.
11. Finn RS, Qin S, Ikeda M, 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(suppl_3): 267.
12. Ren Z, Xu J, Bai Y, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol, 2021, 22(7): 977-990.
13. Akula SM, Abrams SL, Steelman LS, et al. RAS/RAF/MEK/ERK, PI3K/PTEN/AKT/mTORC1 and TP53 pathways and regulatory miRs as therapeutic targets in hepatocellular carcinoma. Expert Opin Ther Targets, 2019, 23(11): 915-929.
14. Kelley RK, Rimassa L, Cheng AL, et al. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol, 2022, 23(8): 995-1008.
15. Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med, 2018, 379(1): 54-63.
16. Qin S, Chan LS, Gu S, et al. LBA35 camrelizumab (C) plus rivoceranib (R) versus sorafenib (S) as first-line therapy for unresectable hepatocellular carcinoma (uHCC): a randomized, phase Ⅲ trial. Ann Oncol, 2022, 33(suppl): 1401-1402.
17. Finn R, Kudo M, Merle P, et al. Primary 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, 2022, 33(suppl_7): S808-S869.
18. Zhang Y, Xu J, Shen J, et al. Update on overall survival (OS) of RESCUE: an open-label, phase 2 trial of camrelizumab (C) in combination with apatinib (A) in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol, 2021, 39(15_suppl): 4076. doi: 10.1200/JCO.2021.39.15_suppl.4076.
19. Xu J, Shen J, Gu S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase Ⅱ trial. Clin Cancer Res, 2021, 27(4): 1003-1011.
20. Finn RS, Ikeda M, Zhu AX, et al. Phase Ⅰb study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol, 2020, 38(26): 2960-2970.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Analysis of targeted therapy combined with immunotherapy for hepatocellular carcinoma

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