Table 8.
Consensus recommendations on biomarkers for patient selection and stratification
| Recommendation | Level of agreement |
|---|---|
| Validated biomarkers predictive of treatment response in HCC across all disease stages remain an unmet need | Strong consensus (100%) |
| Accelerated approval, biomarker-enriched single-arm trials: single-arm phase II studies enriched for a specific biomarker showing substantial clinical activity are an unmet need | Strong consensus (~95%) |
| Regular approval, biomarker-enriched randomized trials: for biomarkers with strong predictive validity in phase II studies, a confirming phase III randomized controlled trial enriched with the same biomarkers should provide the basis of approval compared with the SOC | Strong consensus (100%) |
| Regular approval, biomarker-stratified all-comers trials: when biomarker prediction of outcome in phase II is moderate or has not been explored, a path for approval in phase III trials for all comers should include prespecified biomarker strata, hierarchical hypotheses and explicit a allocation to provide robustness of the signal in the subgroup analysis, while ensuring statistical integrity | Strong consensus (100%) |
| Post-hoc biomarker rescue pathway: if a completed phase III trial is negative overall but a biomarker-defined subgroup shows a large, consistent benefit for the OS end point, a confirmatory phase III study is recommended | Strong consensus (~95%) |
| Future clinical trials should incorporate exploratory biomarkers (blood-based or tissue-based biomarkers) to enhance patient selection, refine stratification and support individualized treatment approaches | Strong consensus (~95%) |
HCC, hepatocellular carcinoma; OS, overall survival; SOC, standard-of-care.