The Current and Prospective Adjuvant Therapies for Hepatocellular Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Risk Factors
2.1. Nature of Liver Cancer Etiology
2.2. Risk Factors for HCC Recurrence
3. Adjuvant Local Treatments
3.1. Transcatheter Arterial Chemoembolization
3.2. Hepatic Arterial Infusion Chemotherapy and Portal Vein Infusion Chemotherapy (PVC)
3.2.1. HAIC in Postoperative Adjuvant Treatment
3.2.2. Portal Vein Infusion Chemotherapy in Postoperative Adjuvant Treatment for HCC with Portal Vein Tumor Thrombosis
3.2.3. Meta-Analysis and Randomized Controlled Trial
3.3. Radiotherapy
4. Adjuvant Systemic Therapy
4.1. Target Therapy
4.1.1. Sorafenib
4.1.2. Apatinib
4.1.3. Lenvatinib
4.2. Immunotherapy
4.3. Chemotherapy
4.3.1. Uracil–Tegafur Adjuvant Chemotherapy
4.3.2. Oral Capecitabine Adjuvant Therapy
4.3.3. Adjuvant Chemotherapy after Liver Transplantation
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
HCC | Hepatocellular carcinoma |
HBV | Hepatitis B virus |
HCV | Hepatitis C virus |
NAFLD | Non-alcoholic fatty liver disease |
MVI | Microvascular invasion |
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Reference | Study Type | Arms and Intervention | Number of Patients | Main Outcome | Conclusion |
---|---|---|---|---|---|
Liu, C., et al. (2016) [8] | Retrospective study | LR vs. LR + TACE | 55 control vs. 62 treatment | Overall: improved 1-year OS with TACE, but no difference in 2- and 3-year DFS rates | For tumor size > 5 cm: improved 1-, 2-, and 3-year DFS. For tumor size ≤ 5 cm: no difference in 1-, 2-, and 3-year DFS |
Ye, J.Z., et al. (2017) [10] | Retrospective study | LR vs. LR + TACE | 260 microvascular invasion (86 in LR +TACE) resection; 259 w/o microvascular invasion (72 in LR + TACE) arm | LR + TACE improved OS and DFS in patients with microvascular invasion but not in patients without microvascular invasion | All patients had BCLC stage A or B |
Liu, Z.H., et al. (2023) [9] | Retrospective study | LR vs. LR + TACE | 421 resected rHCC with MVI-positive patients underwent LR or LR + TACE | Adjuvant TACE provided longer survival for rHCC with MVI when the recurrence time was within 13 months, while not beyond 13 months | For HCC patients with MVI who underwent R0 resection, 13 months may be a reasonable early recurrence time point, and within this interval, postoperative adjuvant TACE may result in longer survival compared with surgery alone |
Chen, W., et al. (2020) [12] | Meta-analysis | LR vs. LR + TACE | 40 studies (10 RCTs and 30 non-RCTs) involving 11,165 patients | PA-TACE was associated with an increased OS and DFS | PA-TACE was beneficial in patients with HCC who were at high risk of postoperative recurrence |
Chen, Z.H., et al. (2019) [15] | Meta-analysis | LR vs. LR + TACE | 12 trials involving 2190 patients | 1-, 3-, and 5-year overall survival (OS) rates favored adjuvant TACE over HR alone. Adjuvant TACE showed better 1-, 3-, and 5-year DFS | Adjuvant TACE may improve OS and DFS for HCC patients with MVI |
Reference | Eligible Patients | Arms and Intervention | Number of Patients | Main Outcome | Conclusion |
---|---|---|---|---|---|
Xia, F., et al. (2016) [35] | BCLC-C stage (LR) | Sorafenib vs. no | 34 treatment vs. 68 control | The tumor recurrence rate was markedly lower in the sorafenib group (15/34, 44.1%) than in the control group (51/68, 75%, p = 0.002). The median disease-free survival was 12 mo in the study group and 10 mo in the control group. | The use of adjuvant sorafenib has been shown to be effective and safe in decreasing hepatocellular carcinoma (HCC) recurrence and extending disease-free and overall survival rates for patients with BCLC-stage C HCC after curative resection. |
Li, J., et al. (2016) [31] | BCLC-C stage with PVI | Sorafenib vs. no | 12 treatment vs. 24 control | The sorafenib group had a significantly longer time to progression (TTP) (29 mo vs. 22 mo, p = 0.041) and a significantly longer median OS (37 mo vs. 30 mo, p = 0.01). | Patients received sorafenib following surgical resection, was well-tolerated, and demonstrated superior outcomes when compared to those who underwent surgery alone. |
Zhang, X.P., et al. (2019) [29] | BCLC 0-A or BCLC B with microvascular invasion (MVI) | Sorafenib vs. no | 147 treatment vs. 581 control | The overall survival (OS) and recurrence-free survival (RFS) were significantly better for patients in the sorafenib group. | Adjuvant sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI. |
Bai, S., et al. (2022) [36] | HBV-related HCC and MVI-positive (LR) | Lenvatinib vs. no | 57 treatment vs. 236 control | The 1-year, 2-year recurrence rates, and survival rates of the lenvatinib group were improved compared to the non-lenvatinib group (15.9%, 43.2% vs. 40.1%, 57.2%, p = 0.002; 85.8%, 71.2% vs. 69.6%, 53.3%, p = 0.009, respectively). | Postoperative adjuvant therapy with lenvatinib was associated with improved long-term prognosis after R0 resection in HBV-related HCC patients with MVI. |
Cai, L., et al. (2020) [37] | High residual alpha-fetoprotein (LR or ablation) | Lenvatinib vs. TACE vs. no | 23 lenvatinib vs. 25 TACE vs. 36 control | 61% (14 out of 23) achieved an alpha-fetoprotein (AFP) response in the lenvatinib (LEN) group. The 1-year recurrence-free survival (RFS) rate was notably higher for patients in the LEN group who attained an AFP response at 71.4% (10 out of 14) compared to 36.0% (9 out of 25) in the transcatheter arterial chemoembolization (TACE) group and 50.0% (18 out of 36) in the control group. The median RFS has not been reached in the LEN, TACE, and control groups. | Lenvatinib (LEN) resulted in an AFP response in 61% of HCCs with persistently elevated AFP levels following surgery or ablation. This response was linked to a significantly increased 1-year recurrence-free survival (RFS). |
Trial | Test Arm | Comparator | Patient Population | Expected Patients Entry | Primary Endpoint | Trial |
---|---|---|---|---|---|---|
CheckMate 9DX | Nivolumab | Placebo | High-risk recurrent HCC after radical resection/ablation | 530 | RFS | NCT03383458 |
KEY?NOTE-937 | Pembrolizuamb | Placebo | Imaging CR after surgical resection/local ablation | 950 | RFS/OS | NCT03867048 |
EMERALD-2 | Durvaluamab + bevacitumab | Placebo | High-risk recurrent HCC after radical resection/ablation | 888 | RFS | NCT03847428 |
Trial | Test Arm | Comparator | Patient Population | Expected Patients Entry | Primary Endpoint |
---|---|---|---|---|---|
LEAP-012 | TACE + lenvatinib + pembrolizuamb | TACE + placebo | Child-Pugh A First treatment (naïve), no extra-hepatic unresectable HCC | 950 | RFS/OS |
CheckMate-74W | TACE + ipilimumab + nivolumab | TACE + placebo | Intermediate stage ECOG 0-1 Beyond Milan and up-to-seven criteria | 765 | Time to TACE progression/OS |
TACE-3 | TACE + nivolumab | TACE alone | Child-Pugh A ECOG 0-1 No extra-hepatic unresectable HCC | 522 | OS/Time to TACE progression |
TALENT-ACE | TACE + atezolizumab + bevacizumab | TACE alone | Child-Pugh A ECOG 0-1, untreated TKIs, ICIs | 342 | TACE PFS/OS |
EMERALD-3 | TACE + durvalumab + tremelimumab +/− lenvatinib | TACE alone | Child-Pugh A ECOG 0-1 | 525 | PFS |
RENO-TACE | Regorafenib + nivolumab | TACE alone | Beyond up-to-seven criteria | 496 | PFS |
ABC-HCC | Atezolizumab + bevacizumab | TACE alone | Child-Pugh A or B7 ECOG 0-1 | 434 | Time to failure of treatment strategy |
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Du, J.-S.; Hsu, S.-H.; Wang, S.-N. The Current and Prospective Adjuvant Therapies for Hepatocellular Carcinoma. Cancers 2024, 16, 1422. https://doi.org/10.3390/cancers16071422
Du J-S, Hsu S-H, Wang S-N. The Current and Prospective Adjuvant Therapies for Hepatocellular Carcinoma. Cancers. 2024; 16(7):1422. https://doi.org/10.3390/cancers16071422
Chicago/Turabian StyleDu, Jeng-Shiun, Shih-Hsien Hsu, and Shen-Nien Wang. 2024. "The Current and Prospective Adjuvant Therapies for Hepatocellular Carcinoma" Cancers 16, no. 7: 1422. https://doi.org/10.3390/cancers16071422