Evolving Treatment of Advanced Hepatocellular Carcinoma in the Asia–Pacific Region: A Review and Multidisciplinary Expert Opinion
Abstract
:Simple Summary
Abstract
1. Introduction
2. Current and Emerging Systemic Therapies in Advanced HCC
3. Healthcare and Reimbursement Systems in the Asia–Pacific Region
4. Expert Opinion: Treating Advanced HCC in the Asia–Pacific Region
4.1. Sorafenib and Lenvatinib Remain First-Line Treatment Choices
4.2. The IMbrave150 Trial Results Are Practice-Changing
4.3. A Snapshot of Advanced HCC: The Different Perspectives of Patients, Physicians, and Payer Systems
4.3.1. The Patient’s Perspective
4.3.2. The Physician’s Perspective
4.3.3. The Payer System’s Perspective
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Country or Region of Origin of the Guideline | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Asia Pacific (APASL) [11] | China [14] |
Hong Kong (HKLCS) [17] |
Japan (JSH) [13] |
Korea (KLCSG) [5] |
Singapore (NCCS) [15] |
Taiwan (TLCA) [16] | ||||||||
Disease features | MVI+ | EHM+ | MVI+ (IIIa) | EHM+ (IIIb) | Int. I or IIa + Vp 1–3 LA IIb or IIIa + Vp 1–3 | EVM (IVa, IVb) Vp 4 or EHM (or both) | MVI+ | EHM+ | MVI+ (IIc, IIIb, IVa) Single Multiple | EHM+ IVa (LN), IVb (others) | MVI+ | EHM+ | MVI+ | EHM+ |
First-line treatment | Systemic therapy, TACE | CP A or B: systemic therapy CP C: best supportive care | TACE ± (MKI or FOLFOX4, LR, RT) | MKI or FOLFOX4 ± (TACE, RT) | IIb or IIIa, CP A: LR | Systemic therapy | TACE, LR, HAIC, MKI | MKI | TACE (SIRT) ± EBRT Sorafenib Lenvatinib | Sorafenib Lenvatinib | SIRT, TACE | Systemic therapy | LR, MKI | Systemic therapy ± (TACE, SIRT, LR) |
Second-line treatment | MKI | MKI | IIb or IIIa, CP B, or IIIb: TACE | (Vp 1–3: LR x 1–3) | (TACE, EBRT) | Systemic therapy | TACE + RT | Chemo-therapy | ||||||
Later line of treatment | (CT, HAIC if MKI failed or not available) | SIRT, HAIC |
Country or Territory | First Line | Second Line (After Sorafenib) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Sor | Len | Atezo + Bev | Cabo | Rego | Ramu | Nivo | Pembro | Nivo + Ipi | Camre | |
China | A, R | A, R | A, NR a | NA, NR | A, R | NA, NR | NA, NR | NA, NR | NA, NR | A, R |
Japan | A, R | A, R | A, R | A, R | A, R | A, R | NA, NR | NA, NR | NA, NR | NA, NR |
Korea | A, R | A, R | A, NR | A, NR | A, R | A, NR | NA, b NR | NA, NR | NA, NR | NA, NR |
Singapore | A, NR | A, NR | A, NR | A, NR | A, NR | A, NR | NA, c NR | NA, c NR | NA, NR | NA, NR |
Taiwan | A, R | A, R | A, NR | A, NR | A, R | A, NR | A, d NR | A, d NR | NA, NR | NA, NR |
Study Drug (s) | Control Arm | Key Eligibility Criteria | Clinical Trials Identifier (Study Name) | Mechanism of Study Drug | Status |
---|---|---|---|---|---|
Atezolizumab + bevacizumab | Sorafenib | ECOG PS ≤1, CP A, ≥1 measurable lesion | NCT03434379 (IMbrave150) | Anti-PDL1 Anti-VEGF | Active, not recruiting |
Lenvatinib + pembrolizumab | Lenvatinib + placebo | ECOG PS ≤1, BCLC stage B or C, CP A, ≥1 measurable lesion | NCT03713593 (LEAP-002) | MKI Anti-PD1 | Active, not recruiting |
Sintilimab + bevacizumab biosimilar IBI305 | Sorafenib | ECOG PS ≤1, BCLC stage B or C, CP score ≤7, ≥1 measurable lesion | NCT03794440 (ORIENT-32) | Anti-PD1 Anti-VEGF | Active, not recruiting |
Cabozantinib + atezolizumab | Sorafenib | ECOG PS ≤1, BCLC stage B or C, CP A, measurable disease | NCT03755791 (COSMIC-312) | Anti-VEGFR Anti-PDL1 | Recruiting |
Camrelizumab (SHR-1210) + apatinib | Sorafenib | ECOG PS ≤1, BCLC stage B or C, CP A, ≥1 measurable lesion | NCT03764293 | Anti-PD1 Anti-VEGFR2 | Recruiting |
Camrelizumab (SHR-1210) + FOLFOX4 | Placebo + FOLFOX4 | ECOG PS ≤1, CP score ≤7, measurable disease | NCT03605706 | Anti-PD1 Chemotherapy | Recruiting |
Durvalumab ± tremelimumab | Sorafenib | ECOG PS ≤1, BCLC stage B or C, CP A | NCT03298451 (HIMALAYA) | Anti-PDL1 Anti-CTLA4 | Recruiting |
IBI310 + sintilimab | Sorafenib | ECOG PS ≤1, BCLC stage B or C, CP score ≤6, ≥1 measurable lesion | NCT04720716 | Anti-CTLA4 Anti-PD1 | Recruiting |
Lenvatinib ± CS1003 | Placebo | ECOG PS ≤1, BCLC stage B or C, CP A, ≥1 measurable lesion | NCT04194775 | MKI Anti-PD1 | Recruiting |
Nivolumab + ipilimumab | Sorafenib or lenvatinib | ECOG PS ≤1, CP A, ≥1 measurable lesion | NCT04039607 (CheckMate 9DW) | Anti-PD1 Anti-CTLA4 | Recruiting |
SCT-I10A + bevacizumab biosimilar SCT-510 | Sorafenib | ECOG PS ≤1, BCLC stage B or C, CP score ≤7, ≥1 measurable lesion | NCT04560894 | Anti-PD1 Anti-VEGF | Recruiting |
HLX10 + HLX04 | Sorafenib | BCLC stage B or C, ≥1 measurable lesion | NCT04465734 | Anti-PD1 Anti-VEGF | Not yet recruiting |
Penpulimab injection + anlotinib | Sorafenib | ECOG PS ≤1, BCLC stage B or C, CP score ≤7, ≥1 measurable lesion | NCT04344158 | Anti-PD1 MKI | Not yet recruiting |
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Ogasawara, S.; Choo, S.-P.; Li, J.-T.; Yoo, C.; Wang, B.; Lee, D.; Chow, P.K.H. Evolving Treatment of Advanced Hepatocellular Carcinoma in the Asia–Pacific Region: A Review and Multidisciplinary Expert Opinion. Cancers 2021, 13, 2626. https://doi.org/10.3390/cancers13112626
Ogasawara S, Choo S-P, Li J-T, Yoo C, Wang B, Lee D, Chow PKH. Evolving Treatment of Advanced Hepatocellular Carcinoma in the Asia–Pacific Region: A Review and Multidisciplinary Expert Opinion. Cancers. 2021; 13(11):2626. https://doi.org/10.3390/cancers13112626
Chicago/Turabian StyleOgasawara, Sadahisa, Su-Pin Choo, Jiang-Tao Li, Changhoon Yoo, Bruce Wang, Dee Lee, and Pierce K. H. Chow. 2021. "Evolving Treatment of Advanced Hepatocellular Carcinoma in the Asia–Pacific Region: A Review and Multidisciplinary Expert Opinion" Cancers 13, no. 11: 2626. https://doi.org/10.3390/cancers13112626