Liver function trajectory and post-progression outcomes in the phase 3 EMERALD-3 study of tremelimumab (T) + durvalumab (D) ± lenvatinib (L) + transarterial chemoembolisation (TACE) in participants (pts) with embolisation-eligible hepatocellular carcinoma (eeHCC)

EMERALD-3

Patient / Population Intervention / Exposition Vergleich Endpunkt

In people with embolisation-eligible hepatocellular carcinoma across baseline liver function grades, tremelimumab plus durvalumab with or without lenvatinib added to TACE numerically improved post-progression survival and time to next treatment compared with TACE alone while liver function remained stable over treatment.

N

—Patienten

Design

Phase 3 randomised trial in adults with embolisation-eligible hepatocellular carcinoma, allocated 1:1:1 and then 1:1 to tremelimumab plus durvalumab (STRIDE) with lenvatinib plus TACE, STRIDE plus TACE, or TACE alone, stratified by region, prior palliative embolisation and baseline tumour burden, reported here as a post-hoc exploratory analysis by baseline ALBI grade (NCT05301842).

Endpunkt

Primary endpoint PFS for STRIDE plus lenvatinib plus TACE vs TACE. This post-hoc exploratory analysis reports liver function trajectory (ALBI and Child-Pugh scores) and OS, PFS2 and time to next treatment by baseline ALBI grade.

ErgebnisThe trial met its primary PFS endpoint, but no PFS figures are given here. In ALBI grade 1, median OS was 44.6 mo (95% CI 39.5-NC) with STRIDE + lenvatinib + TACE vs 39.2 mo (34.7-NC) with TACE (HR 0.86, 95% CI 0.60-1.22). In grade 2/3 it was 28.5 mo (20.7-34.3) vs 22.1 mo (17.4-33.3) (HR 0.88, 0.60-1.28). For STRIDE + TACE vs TACE, median OS was NC (37.8-NC) vs 39.2 mo (28.0-NC) in grade 1 (HR 0.57, 95% CI 0.36-0.90) and 27.9 mo (17.8-NC) vs 20.4 mo (16.6-30.1) in grade 2/3 (HR 0.81, 0.52-1.26). PFS2 HR in grade 1 was 0.70 (0.51-0.95) for STRIDE + lenvatinib + TACE and 0.53 (0.36-0.79) for STRIDE + TACE. In grade 2/3 it was 0.74 (0.52-1.05) and 0.69 (0.46-1.05). Time to next treatment HR in grade 1 was 0.56 (0.43-0.72) and 0.46 (0.33-0.64). In grade 2/3 it was 0.57 (0.41-0.77) and 0.55 (0.38-0.80). Mean ALBI and Child-Pugh scores were stable over the treatment period across baseline grades. Subsequent treatment use was 43% (grade 1) and 46% (grade 2/3) with STRIDE + lenvatinib + TACE, 50% and 53% with STRIDE + TACE, and 72% and 68% with TACE. Maximum grade 3/4 TRAEs in grade 1 occurred in 62% vs 18% (STRIDE + lenvatinib + TACE vs TACE) and 47% vs 20% (STRIDE + TACE vs TACE). In grade 2/3 they occurred in 64% vs 20% and 51% vs 27%.

Kudo M, Abou-Alfa GK, Ren Z, et al. Presented at ESMO Congress 2026, abstract LBA48, 24 October. Not yet published.

Diskussion & Kritik

This post-hoc exploratory subgroup analysis by baseline ALBI grade was not powered for comparison, and the abstract does not report the primary PFS result. OS is immature, with several medians and upper confidence limits not calculable. Most OS hazard ratios have confidence intervals crossing 1, apart from STRIDE plus TACE in ALBI grade 1, and the STRIDE plus TACE comparisons use only the first 175 TACE patients. Liver function stability is described only as stable mean scores with no figures. The 'comparable safety' claim refers to consistency across baseline grades: grade 3/4 TRAEs were roughly two to three times as frequent with the STRIDE-based arms as with TACE. Blinding is not reported.