Systemic treatments for advanced HCC: a comparative analysis of efficacy, survival outcomes, and safety profiles
| Drug | Target | Benefits | Median OS and hazard ratio | Common adverse effects | Reference |
|---|---|---|---|---|---|
| Sorafenib | TKI—VEGFR, PDGFR, RAF | First-line for advanced HCC, delays HCC progression | 6.5 months (5.56–7.56) and 0.68 | HFSR, diarrhea, fatigue, hypertension | [36] |
| Donafenib | TKI—RAF/MEK/ERK | Modified structure of sorafenib | 12.1 months and 0.831 | HFSR, diarrhea, and elevated LFT | [42] |
| Lenvatinib | TKI—VEGFR, FGFR, PDGFR, RET, KIT | Non-inferior to sorafenib, higher response rate (24%) | 13.6 months (range from 12.1–14.9) and 0.92 | Palmar-plantar erythrodysesthesia, hypertension, weight loss, proteinuria, diarrhea | [43] |
| Regorafenib | TKI—VEGFR, PDGFR, FGFR | Second-line after sorafenib, OS benefit (~ 3 months) | 10.6 months (range from 9.1–12.1) and 0.63 | Fatigue, diarrhea, hypertension, HFSR | [38] |
| Cabozantinib | TKI—MET, VEGFR, AXL | Second/Third-line, OS and PFS benefit, activity in bone/lung metastases | 10.2 months and 0.76 | Diarrhea, HFSR, fatigue, increased LFTs | [44] |
| Ramucirumab | Anti-VEGFR-2 monoclonal antibody | Second-line if AFP > 400 ng/mL, improves OS in AFP-high HCC | 8.5 months (range from 7.0–10.6) and 0.710 | Hypertension, proteinuria, bleeding, fatigue | [45] |
| Apatinib | TKI of VEGFR-2 | Second-line treatment after chemotherapy failure | 8.7 months (range from 7.5–9.8) and 0.785 | Hypertension, HFSR | [46] |
| FOLFOX (5-FU + leucovorin + oxaliplatin) | Cytotoxic chemotherapy | Some benefit in Asia, used in advanced/metastatic HCC | 5.9 months and 0.75 | Hematological symptoms, diarrhea, neuropathy | [47] |
| Nivolumab + ipilimumab | Checkpoint inhibitors (PD-1 + CTLA-4) | Active in metastatic HCC | 23.7 months (range from 18.8–29.4) and 0.76 | Hepatitis-colitis, endocrinopathies, skin rash | [48] |
| Atezolizumab + bevacizumab | PD-L1 + VEGF inhibition | First-line standard in advanced HCC | 19.2 months (range from 17.0–23.7) and 0.66 | Hypertension, GI bleed, fatigue, immune hepatitis | [40] |
5-FU: 5-fluorouracil; AFP: alpha-fetoprotein; GI: gastrointestinal; HCC: hepatocellular carcinoma; HFSR: hand-foot skin reaction; LFT: liver function test; OS: overall survival; PD-1: programmed death-1; PD-L1: programmed death-ligand 1; PFS: progression-free survival; TKI: tyrosine kinase inhibitor; VEGF: vascular endothelial growth factor; VEGFR: VEGF receptor
We also extend our utmost gratitude to Dr. Dinesh Kumar Meena, Research Scientist-II, St John’s Research Institute, Bangalore, for his invaluable insights and feedback on this manuscript.
MKN: Writing—original draft. DS and BV: Writing—review & editing.
The authors declare that there are no conflicts of interest.
This article is a review of previously published studies and does not involve human participants, animal subjects, or the collection of primary data; therefore, ethical approval was not required.
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This article is a review of previously published studies, and no new data were generated or analyzed in the course of this study. All data supporting the findings of this article are available in the cited references.
This work was supported by the JIPMER intramural research grant [JIP/Res/Intramural/Phase-4/2023-2024]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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