Table.
Summary of approved and available systemic therapies for hepatocellular carcinoma
| Agent | Trial | n | Comparator arm | Study population | Median OS (months) | HR | Remarks and recommendation |
|---|---|---|---|---|---|---|---|
| First-line | |||||||
| Sorafenib | SHARP trial28 Phase III | 602 | Placebo BSC | Not eligible or progressed after surgical or locoregional therapies. >90% - Child-Pugh A. 70% had microvascular invasion, extrahepatic spread or both. | 10.7 vs. 7.9 | 0.69 | One-year survival rate was 44 vs. 33%. Response rate was low, only two patients had PR with sorafenib. Recommended |
| Sorafenib | Asia-Pacific study35 Phase III | 226 (2:1) | BSC | Patients were young. Rest similar to SHARP trial | 6.5 vs. 4.2 | 0.68 | |
| Atezolizumab + Bevacizumab | IMbrave trial30
Phase III |
501 | Sorafenib | unresectable hepatocellular carcinoma who had not previously received systemic treatment, Child Pugh A ECOG PS <=1 | Not reached vs 13.2 mo | 0.58 | 1-y OS was 67.2% (95% CI, 61.3 to 73.1) with atezolizumab-bevacizumab and 54.6% (95% CI, 45.2 to 64.0) with sorafenib. Approved for first-line therapy |
| Lenvatinib | REFLECT trial34
Phase III Noninferiority |
954 | Sorafenib | Asia-pacific, Europe, North-America. ECOG PS 0, 1 Child-Pugh A | 12.3 vs. 13.6 | 0.92 | Approved for first-line therapy (previous systemic therapy was not allowed in the trial) |
| Second-line post sorafenib | |||||||
| Regorafenib | RESORCE29 Phase III trial | 573 | Placebo | Child-Pugh A | 10.6 vs. 7.8 | 0.63 | Response rate with regorafenib was 11%; 7 deaths due to regorafenib. Recommended for postsorafenib |
| Ramucirumab | REACH36
Phase III |
292 | Placebo BSC | AFP ≥400 ng/ml | 8.5 vs. 7.3 | 0.71 | Pooled analysis from REACH and REACH-2 - OS 8.1 vs. 5 months |
| Nivolumab | Phase I/II32 | 48/214 | - | 13.2 | Six month OS rate - 75%* |
Cabozantinib is approved in second-line setting (not available in India at the time of writing this manuscript). *Recommendation of nivolumab in second-line is based on Phase 2 trial. However, pembrolizumab Phase 3 trial in this setting is negative. OS, overall survival; HR, hazard ratio; BSC, best supportive care; ECOG PS, Eastern Cooperative Oncology Group performance status; AFP, alpha foetoprotein