Tremelimumab plus durvalumab improves survival in Asians with unresectable HCC

A single tremelimumab regular interval durvalumab (STRIDE) provides survival benefits to Asian patients with unresectable hepatocellular carcinoma (HCC), as shown by the results of the HIMALAYA study.

“[T]hese results support the benefit of STRIDE for participants with unresectable HCC in the Asia Pacific region and continue to support the positive benefit-risk profile of this regimen in a diverse population, reflective of unresectable HCC globally,” the investigators said.

The Asian subgroup in the HIMALAYA study consisted of 479 participants, who were randomly assigned to receive STRIDE (n=156), durvalumab (n=167), or sorafenib (n=156). This subgroup included patients enrolled in Hong Kong, India, South Korea, Taiwan, Thailand, and Vietnam.

The investigators assessed overall survival (OS), objective response rate (ORR; per RECIST, version 1.1), and safety in Asians and in an exploratory subgroup of participants in Hong Kong and Taiwan (n=141).

STRIDE resulted in significant OS improvements as compared with sorafenib (hazard ratio [HR], 0.68, 95 percent confidence interval [CI], 0.52–0.89). In addition, durvalumab also improved OS relative to sorafenib (HR, 0.83, 95 percent CI, 0.64–1.06). [J Hepatol 2025;82:258-267]

In the exploratory subgroup, STRIDE also provided OS benefits when compared with sorafenib (HR, 0.44, 95 percent CI, 0.26–0.77), as did durvalumab (HR, 0.64, 95 percent CI, 0.37–1.08).

ORR, including unconfirmed responses, in the Asian subgroup was numerically higher in the STRIDE and durvalumab arms compared with the sorafenib arm (28.2 percent and 18.6 percent vs 9.0 percent).

With regard to safety, the proportion of patients experiencing serious treatment-related adverse events (grade 3/4) was lower with STRIDE and durvalumab than with sorafenib (19.9 percent and 13.3 percent vs 30.5 percent).

“The trial showed a benefit for participants treated with STRIDE compared with sorafenib across clinically relevant subgroups,” the investigators said. “Findings from this exploratory analysis of the Asian subgroup of participants in HIMALAYA continue to support the efficacy of STRIDE across geographic regions.” [NEJM Evid 2022;1:EVIDoa2100070; Ann Oncol 2024;35:448-457]

Global cohort

The HIMALAYA study did not include participants from mainland China as part of the global study, but the global cohort of the IMbrave150 study consisted of a substantial proportion of individuals from mainland China who were predominantly hepatitis B virus (HBV)-infected. [Liver Cancer 2021;10:296-308; N Engl J Med 2020;382:1894-1905]

Results of the exploratory analysis in both the Asian and Hong Kong and Taiwan subgroups of HIMALAYA were consistent with those in the global and Chinese cohorts of IMbrave150.

"Overall, these outcomes support the improved clinical benefit of immunotherapy-containing regimens, in particular, when compared with sorafenib, including in subsets of Asian patients and in those who are HBV positive,” the investigators said.

“Therefore, overall outcomes for global studies are likely influenced by the relative representation of geographic subgroups, posing limitations for the interpretation of cross-trial comparisons,” they added.

In the global, phase III HIMALAYA study, STRIDE improved OS when compared with sorafenib, while durvalumab showed noninferiority to sorafenib. HBV is the most common HCC aetiology in Asia, except in Japan, according to the investigators.