When a hazard ratio is not enough: non-proportional hazards are reshaping the interpretation of phase III trials in hepatocellular carcinoma

Erica Villa

Hepatoma Research ›› 2026, Vol. 12 : 38

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Hepatoma Research ›› 2026, Vol. 12:38 DOI: 10.20517/2394-5079.2026.49
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When a hazard ratio is not enough: non-proportional hazards are reshaping the interpretation of phase III trials in hepatocellular carcinoma
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Erica Villa. When a hazard ratio is not enough: non-proportional hazards are reshaping the interpretation of phase III trials in hepatocellular carcinoma. Hepatoma Research, 2026, 12: 38 DOI:10.20517/2394-5079.2026.49

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References

[1]

Mauro E,de Castro T,Zeitlhoefler M.et al. Strategies to address non-proportional hazards between survival curves - Lessons from phase III trials in hepatocellular carcinoma J Hepatol 2026 84 567 77 PMC13188190

[2]

Grambsch PM,Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals Biometrika 1994 81 515 26

[3]

Royston P,Parmar MK. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt Stat Med 2011 30 2409 21

[4]

Uno H,Claggett B,Tian L.et al. Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis J Clin Oncol 2014 32 2380 5 PMC4105489

[5]

Eggermont AMM,Robert C,Ribas A. The new era of adjuvant therapies for melanoma Nat Rev Clin Oncol 2018 15 535 6

[6]

Pang H,Yang G,Ho JC.et al. Assessing surrogacy using restricted mean survival time ratio for overall survival in non-small cell lung cancer immunotherapy studies. Chin Clin Oncol. 2022;11:7

[7]

Yopp A,Kudo M,Chen M.et al. LBA39 updated efficacy and safety data from IMbrave050: phase III study of adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients (pts) with resected or ablated high-risk hepatocellular carcinoma (HCC) Ann. Oncol. 2024 35 S1230

[8]

Kudo M,Ren Z,Guo Y.et al. ; LEAP-012 investigators. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study Lancet 2025 405 203 15

[9]

Abou-Alfa GK,Lau G,Kudo M.et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma NEJM Evid 2022 1 EVIDoa2100070

[10]

Rimassa L,Chan SL,Sangro B.et al. Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC J Hepatol 2025 83 899 908

[11]

Yau T,Galle PR,Decaens T.et al. ; CheckMate 9DW investigators. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial Lancet 2025 405 1851 64

[12]

International Council for Harmonisation. ICH E9(R1): Addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials. Available from: https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf. [Last accessed on 3 Jul 2026]

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