Outcomes by Comorbidities with Tremelimumab and Durvalumab in the Randomized, Controlled Phase 3 HIMALAYA Study in Unresectable Hepatocellular Carcinoma.
12 affiliations
- 1Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
- 2Hepatopancreatobiliary Oncology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Italy.
- 3Department of Medicine, Division of Hematology/Oncology, University of California Irvine, Orange, CA, USA.
- 4Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
- 5Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
- 6State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Sir Yue-Kong Pao Center for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.
- 7Global Medical Affairs, AstraZeneca, Cambridge, UK.
- 8Oncology R&D, AstraZeneca, Cambridge, UK.
- 9Oncology R&D, Late-Stage Development, AstraZeneca, Cambridge, UK.
- 10Department of Medicine, Memorial Sloan Kettering Cancer Center, Cornell University, New York, NY, USA.
- 11Weill Medical College, Cornell University, New York, NY, USA.
- 12Trinity College Dublin, Dublin, Ireland.
Abstract
Introduction
People with hepatocellular carcinoma (HCC) often have underlying comorbidities, which may impact prognosis and lead to safety challenges following treatment. This exploratory, post hoc analysis of the phase 3 HIMALAYA study (NCT03298451) assessed outcomes in participants with unresectable HCC and cardiovascular or metabolic comorbidities at baseline.Methods
Participants with unresectable HCC were randomized to STRIDE (Single Tremelimumab Regular Interval Durvalumab), durvalumab monotherapy, or sorafenib. Comorbidities were based on medical history assessed at baseline and qualified using preferred terms from cardiovascular or metabolic Standardised Medical Dictionary for Regulatory Activities Queries. Overall survival (OS) rates were evaluated in participants with or without cardiovascular or metabolic comorbidities within and by treatment group. The proportion of long-term survivors (alive ≥36 months post-randomization) and safety were assessed in participants with cardiovascular or metabolic comorbidities. Data cutoffs: August 27, 2021 (primary analysis); January 23, 2023 (4-year updated analysis, OS, and serious treatment-related adverse events).Results
Hypertension and type 2 diabetes mellitus were the most common cardiovascular and metabolic comorbidities, respectively. The 48-month OS rates with STRIDE were 28.0% and 21.7% in participants with and without cardiovascular comorbidities and 20.4% and 28.5% in those with and without metabolic comorbidities, respectively. In total, 28.2% of participants with cardiovascular comorbidities and 22.6% of participants with metabolic comorbidities experienced long-term survival with STRIDE. Safety in participants with cardiovascular or metabolic comorbidities was generally consistent with all participants in the safety analysis set; no new safety signals were observed.Conclusions
OS benefits with STRIDE were similar in participants with vs. without cardiovascular or metabolic comorbidities, with manageable safety in participants with comorbidities. These results support the durable benefits of STRIDE in a broad population reflective of unresectable HCC globally.
Related
- A Case of Unresectable Hepatocellular Carcinoma Responding to Durvalumab Plus Tremelimumab after Lenvatinib Treatment
- Immune-mediated Myocarditis after Durvalumab/tremelimumab Treatment for Unresectable Hepatocellular Carcinoma
- Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma
- An integrated Phase II/III randomized study comparing durvalumab and tremelimumab ± Hepatic ArteriaL infusion chemotherapy with GEMOX in hepatocellular Carcinoma with high tumor burdEn – ALICE (PRODIGE89 – UCGI44 – ALICE)
- An Effective Case of Radiofrequency Ablation with the Combination of Durvalumab and Tremelimumab Treatment for Hepatocellular Carcinoma
BibTeX
@article{rimassa2026outcomes,
title = {{Outcomes by Comorbidities with Tremelimumab and Durvalumab in the Randomized, Controlled Phase 3 HIMALAYA Study in Unresectable Hepatocellular Carcinoma.}},
author = {Lorenza Rimassa and Farshid Dayyani and Robin K Kelley and Bruno Sangro and Stephen L Chan and Hitomi Nakamura and Lucy Clark and Ioannis Xynos and Ghassan K Abou-Alfa},
journal = {Liver cancer},
year = {2026},
month = jul,
doi = {10.1159/lic/admag001},
url = {https://europepmc.org/article/MED/42924082},
note = {CC BY},
}
RIS
TY - JOUR
TI - Outcomes by Comorbidities with Tremelimumab and Durvalumab in the Randomized, Controlled Phase 3 HIMALAYA Study in Unresectable Hepatocellular Carcinoma.
AU - Lorenza Rimassa
AU - Farshid Dayyani
AU - Robin K Kelley
AU - Bruno Sangro
AU - Stephen L Chan
AU - Hitomi Nakamura
AU - Lucy Clark
AU - Ioannis Xynos
AU - Ghassan K Abou-Alfa
PY - 2026
DA - 2026/07/28
JO - Liver cancer
DO - 10.1159/lic/admag001
UR - https://europepmc.org/article/MED/42924082
AB - Introduction People with hepatocellular carcinoma (HCC) often have underlying comorbidities, which may impact prognosis and lead to safety challenges following treatment. This exploratory, post hoc analysis of the phase 3 HIMALAYA study (NCT03298451) assessed outcomes in participants with unresectable HCC and cardiovascular or metabolic comorbidities at baseline.Methods Participants with unresectable HCC were randomized to STRIDE (Single Tremelimumab Regular Interval Durvalumab), durvalumab monotherapy, or sorafenib. Comorbidities were based on medical history assessed at baseline and qualified using preferred terms from cardiovascular or metabolic Standardised Medical Dictionary for Regulatory Activities Queries. Overall survival (OS) rates were evaluated in participants with or without cardiovascular or metabolic comorbidities within and by treatment group. The proportion of long-term survivors (alive ≥36 months post-randomization) and safety were assessed in participants with cardiovascular or metabolic comorbidities. Data cutoffs: August 27, 2021 (primary analysis); January 23, 2023 (4-year updated analysis, OS, and serious treatment-related adverse events).Results Hypertension and type 2 diabetes mellitus were the most common cardiovascular and metabolic comorbidities, respectively. The 48-month OS rates with STRIDE were 28.0% and 21.7% in participants with and without cardiovascular comorbidities and 20.4% and 28.5% in those with and without metabolic comorbidities, respectively. In total, 28.2% of participants with cardiovascular comorbidities and 22.6% of participants with metabolic comorbidities experienced long-term survival with STRIDE. Safety in participants with cardiovascular or metabolic comorbidities was generally consistent with all participants in the safety analysis set; no new safety signals were observed.Conclusions OS benefits with STRIDE were similar in participants with vs. without cardiovascular or metabolic comorbidities, with manageable safety in participants with comorbidities. These results support the durable benefits of STRIDE in a broad population reflective of unresectable HCC globally.
SN - 2235-1795
SN - 1664-5553
ER -