Subsequent anticancer therapy analysis of the Phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma

Background and Aims: In the Phase 3 HIMALAYA study (NCT03298451), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) vs sorafenib in participants (pts) with unresectable hepatocellular carcinoma (uHCC; Abou-Alfa et al. NEJM Evid 2022). The OS benefit with STRIDE persisted after 5 years of follow-up (OS HR 95% confidence interval [CI] vs sorafenib, 0.76 [0.65–0.89]; Rimassa et al. oral presentation (974MO) at ESMO 2024). Assessment of subsequent anticancer therapy (SAT) use is key to understanding the long-term benefits and outcomes of STRIDE. Here, we report the assessment of SAT use at the 5-year follow-up.

Method: Pts with uHCC were randomised to STRIDE, durvalumab monotherapy or sorafenib. SAT use, time to first subsequent treatment or death (TFST) and OS in the STRIDE and sorafenib arms were assessed. Data cut-off was 1 Mar 2024.

Results: Median (95% CI) duration of follow-up was 62.49 (59.47–64.79) months (m) for STRIDE and 59.86 (58.32–61.54) m for sorafenib. Of 1171 pts randomised, 168/393 (42.7%) pts in the STRIDE arm and 179/389 (46.0%) pts in the sorafenib arm received SATs, and 20/393 (5.1%) pts in the STRIDE arm and 6/389 (1.5%) pts in the sorafenib arm remained on initial study treatment. Subsequent immunotherapy use was higher in the sorafenib arm (94/389 [24.2%] pts) than the STRIDE arm (25/393 [6.4%] pts) at 60 m, while targeted therapy use was higher in the STRIDE arm (155/393 [39.4%]) than the sorafenib arm (112/389 [28.8%]); subsequent chemotherapy use was similar between the STRIDE arm (24/393 [6.1%]) and sorafenib arm (27/389 [6.9%]). Median (95% CI) TFST was longer for STRIDE vs sorafenib (8.44 [7.23–10.22] m vs 7.13 [5.98–7.95] m; HR, 0.77; 95% CI, 0.66–0.89). Median (95% CI) OS was numerically longer for STRIDE vs sorafenib in pts with SAT use (26.7 [20.7–30.2] m vs 20.9 [16.9–24.4] m; HR, 0.80; 95% CI, 0.64–1.01) and without SAT use (10.7 [8.7–14.3] m vs 8.1 [6.3–10.3] m; HR, 0.71; 95% CI, 0.58–0.88). OS benefit with STRIDE was consistent after censoring pts at initiation of any SAT (OS HR [95% CI], 0.74 [0.60–0.92]).

Conclusion: STRIDE maintained longer OS vs sorafenib, regardless of SAT use, further supporting its independent and sustained effect on pt survival. Furthermore, delayed TFST with STRIDE provides an additional measure of effectiveness for STRIDE in addition to its effect on pt survival.

This abstract was originally presented at the EASL 2025.

Publikationsverlauf

Artikel online veröffentlicht:
04. September 2025