Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma

George Lau; Ghassan K Abou-Alfa; Ann-Lii Cheng; Wattana Sukeepaisarnjaroen; Tu Van Dao; Yoon Koo Kang; Satheesh Chiradoni Thungappa; Masatoshi Kudo; Bruno Sangro; Robin Kate Kelley; Junji Furuse; Joong-Won Park; Patrapim Sunpaweravong; Angelica Fasolo; Thomas Yau; Tomokazu Kawaoka; Sergio Azevedo; Maria Reig; Eric Assenat; Mark Yarchoan; Aiwu Ruth He; Mallory Makowsky; Charu Gupta; Alejandra Negro; Stephen L Chan

doi:10.1016/j.jhep.2024.07.017

Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma

J Hepatol. 2024 Jul 31:S0168-8278(24)02424-3. doi: 10.1016/j.jhep.2024.07.017. Online ahead of print.

Authors

George Lau¹, Ghassan K Abou-Alfa², Ann-Lii Cheng³, Wattana Sukeepaisarnjaroen⁴, Tu Van Dao⁵, Yoon Koo Kang⁶, Satheesh Chiradoni Thungappa⁷, Masatoshi Kudo⁸, Bruno Sangro⁹, Robin Kate Kelley¹⁰, Junji Furuse¹¹, Joong-Won Park¹², Patrapim Sunpaweravong¹³, Angelica Fasolo¹⁴, Thomas Yau¹⁵, Tomokazu Kawaoka¹⁶, Sergio Azevedo¹⁷, Maria Reig¹⁸, Eric Assenat¹⁹, Mark Yarchoan²⁰, Aiwu Ruth He²¹, Mallory Makowsky²², Charu Gupta²³, Alejandra Negro²², Stephen L Chan²⁴

Affiliations

¹ Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong Special Administrative Region, China.
² Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA; Weill Medical College, Cornell University, New York, New York, USA. Electronic address: [email protected].
³ National Taiwan University Cancer Center, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand.
⁵ Cancer Research and Clinical Trials Center, Department of Optimal Therapy, National Cancer Hospital, Hanoi, Vietnam.
⁶ Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
⁷ Sri Venkateshwara Hospital, Bangalore, India.
⁸ Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
⁹ Liver Unit and HPB Oncology Area, Cancer Center Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
¹⁰ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
¹¹ Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
¹² Department of Gastroenterology and Hepatology, Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea.
¹³ Department of Internal Medicine, Prince of Songkla University Hospital, Songkhla, Thailand.
¹⁴ Fondazione Michelangelo, Milan, Italy.
¹⁵ Queen Mary Hospital, Pok Fu Lam, Hong Kong Special Administrative Region, China.
¹⁶ Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan.
¹⁷ Department of Internal Medicine, UPCO-Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
¹⁸ Barcelona Clinic Liver Cancer (BCLC), Liver Oncology Unit, Liver Unit, Hospital Clinic de Barcelona, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain.
¹⁹ Department of Medical Oncology, Saint Eloi Hospital, Montpellier University, Montpellier, France.
²⁰ Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
²¹ Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA.
²² AstraZeneca, Gaithersburg, Maryland, USA.
²³ AstraZeneca, Wilmington, Delaware, USA.
²⁴ State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Sir Yue-Kong Pao Center for Cancer, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

PMID: 39089633
DOI: 10.1016/j.jhep.2024.07.017

Abstract

Background & aims: In the global, phase III HIMALAYA study in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) vs. sorafenib; durvalumab was non-inferior to sorafenib. HBV is the predominant HCC aetiology in most of Asia vs. HCV or non-viral aetiologies in Western countries and Japan. This analysis evaluated safety and efficacy outcomes for STRIDE and durvalumab monotherapy vs. sorafenib, in HIMALAYA participants enrolled in Asia, excluding Japan.

Methods: In HIMALAYA, participants were randomised to STRIDE, durvalumab, or sorafenib. The Asian subgroup in this analysis included participants enrolled in Hong Kong, India, South Korea, Taiwan, Thailand, and Vietnam. OS, objective response rate (ORR; per RECIST, version 1.1), and safety were assessed in the Asian subgroup and in an exploratory subgroup of participants in Hong Kong and Taiwan.

Results: The Asian subgroup included 479 participants randomised to STRIDE (n = 156), durvalumab (n = 167), or sorafenib (n = 156). OS was improved for STRIDE vs. sorafenib (hazard ratio [HR] 0.68; 95% CI 0.52-0.89). The OS HR for durvalumab vs. sorafenib was 0.83 (95% CI 0.64-1.06). In Hong Kong and Taiwan (n = 141), OS HRs for STRIDE vs. sorafenib and durvalumab vs. sorafenib were 0.44 (95% CI 0.26-0.77) and 0.64 (95% CI 0.37-1.08), respectively. In the Asian subgroup, ORR (including unconfirmed responses) was numerically higher for STRIDE (28.2%) and durvalumab (18.6%) vs. sorafenib (9.0%), and Grade 3/4 treatment-related adverse events were numerically lower for STRIDE (19.9%) and durvalumab (13.3%) vs. sorafenib (30.5%).

Conclusions: STRIDE improved outcomes vs. sorafenib in the Asian subgroup. These results support the benefits of STRIDE for participants with uHCC globally, including in the Asia-Pacific region.

Clinical trial number: NCT03298451.

Impact and implications: The global, phase III HIMALAYA study found that the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen improved overall survival (OS), including long-term OS vs. sorafenib, and that durvalumab monotherapy was non-inferior to sorafenib in participants with unresectable hepatocellular carcinoma (uHCC). However, there are differences in the aetiology and clinical practices related to HCC in parts of Asia, compared to Western countries and Japan, which could lead to differences in treatment outcomes between these regions. The results of this analysis demonstrate the benefits of STRIDE for participants in the Asia-Pacific region, consistent with the full, global study population. Overall, these findings continue to support the use of STRIDE in a diverse population, reflective of uHCC globally.

Keywords: Asia; Efficacy; Immune checkpoint inhibitor; Safety; Unresectable hepatocellular carcinoma.

Associated data

ClinicalTrials.gov/NCT03298451