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Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma
Open accessAbstract
BACKGROUND: A single, high priming dose of tremelimumab (anti-cytotoxic T lymphocyte–associated antigen 4) plus durvalumab (anti–programmed cell death ligand-1), an infusion regimen termed STRIDE (Single Tremelimumab Regular Interval Durvalumab), showed encouraging clinical activity and safety in a phase 2 trial of unresectable hepatocellular carcinoma. METHODS: In this global, open-label, phase 3 trial, the majority of the patients we enrolled with unresectable hepatocellular carcinoma and no previous systemic treatment were randomly assigned to receive one of three regimens: tremelimumab (300 mg, one dose) plus durvalumab (1500 mg every 4 weeks; STRIDE), durvalumab (1500 mg every 4 weeks), or sorafenib (400 mg twice daily). The primary objective was overall survival for STRIDE versus sorafenib. Noninferiority for overall survival for durvalumab versus sorafenib was a secondary objective. RESULTS: In total, 1171 patients were randomly assigned to STRIDE (n=393), durvalumab (n=389), or sorafenib (n=389). The median overall survival was 16.43 months (95% confidence interval [CI], 14.16 to 19.58) with STRIDE, 16.56 months (95% CI, 14.06 to 19.12) with durvalumab, and 13.77 months (95% CI, 12.25 to 16.13) with sorafenib. Overall survival at 36 months was 30.7%, 24.7%, and 20.2%, respectively. The overall survival hazard ratio for STRIDE versus sorafenib was 0.78 (96.02% CI, 0.65 to 0.93; P=0.0035). Overall survival with durvalumab monotherapy was noninferior to sorafenib (hazard ratio, 0.86; 95.67% CI, 0.73 to 1.03; noninferiority margin, 1.08). Median progression-free survival was not significantly different among all three groups. Grade 3/4 treatment-emergent adverse events occurred for 50.5% of patients with STRIDE, 37.1% with durvalumab, and 52.4% with sorafenib. CONCLUSIONS: STRIDE significantly improved overall survival versus sorafenib. Durvalumab monotherapy was noninferior to sorafenib for patients with unresectable hepatocellular carcinoma. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03298451.)
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“The response rate was 20% with durvalumab plus tremelimumab and 30% with atezolizumab plus bevacizumab, with median duration of response ranging from 18 months to 22 months.”
From Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial (2025) · cites this paper as [7]
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“PD-L1 inhibitor-based regimens received approvals in 2020 (atezolizumab plus bevacizumab) and 2022 (tremelimumab plus durvalumab) as first-line treatment options for unresectable hepatocellular carcinoma after showing improved outcomes over sorafenib, with median overall survival ranging from 16 months to 19 months.”
From Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial (2025) · cites this paper as [7]
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“With the introduction of PD-L1 inhibitors in this setting, survival benefits versus sorafenib were improved with a median overall survival of 19•2 months with atezolizumab plus bevacizumab, 9,10 16•6 months with durvalumab monotherapy, and 16•4 months with tremelimumab plus durvalumab, 7,8 leading to regulatory”
From Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial (2025) · cites this paper as [7]
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“At the RP2D, the safety profile was consistent with the known safety profile of durvalumab in combination with tremelimumab in adult patients (13, 14), and no new safety signals were identified in our pediatric population.”
From Phase I/II, open-label, multicenter study of durvalumab in combination with tremelimumab in pediatric patients with advanced solid tumors (2026) · cites this paper as [14]
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“durvalumab plus tremelimumab has demonstrated improved OS compared with sorafenib alone in adults with unresectable hepatocellular cancer (14).”
From Phase I/II, open-label, multicenter study of durvalumab in combination with tremelimumab in pediatric patients with advanced solid tumors (2026) · cites this paper as [14]
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“In HIMALAYA, durvalumab plus tremelimumab yielded an objective response rate of 20% and median duration of response of 22•3 months.7”
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“up to 20% of OBIs may be negative for both HBsAg and hepatitis B core antibody (anti-HBc) with existing assays [67, 68]”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [68]
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BackgroundInfluentialManagement of Hepatocellular Carcinoma
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Metadata
- Authors
- Abou-Alfa, G. K., Lau, G., Kudo, M., Chan, S. L., Kelley, R. K., Furuse, J., Sukeepaisarnjaroen, W., Kang, Y.-K., Van Dao, T., De Toni, E. N., Rimassa, L., Breder, V., Vasilyev, A., Heurgué, A., Tam, V. C., Mody, K., Thungappa, S. C., Ostapenko, Y., Yau, T., Azevedo, S., Varela, M., Cheng, A.-L., Qin, S., Galle, P. R., Ali, S., Marcovitz, M., Makowsky, M., He, P., Kurland, J. F., Negro, A., & Sangro, B.
- Affiliations
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
- Humanity & Health (CN)
- Kindai University Hospital (JP)
- Chinese University of Hong Kong (HK)
- University of California, San Francisco (US)
- Kyorin University (JP)
- Khon Kaen University (TH)
- Asan Medical Center (KR)
- Cancer Research and Clinical Trials Center, Department of Optimal Therapy, National Cancer Hospital, Hanoi, Vietnam
- Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
- Humanitas University (IT)
- Russian Cancer Research Center NN Blokhin (RU)
- Department of Oncology, Railway Clinical Hospital, St. Petersburg, Russia
- Department of Hepato-Gastroenterology, Robert-Debré Hospital, Reims, France
- University of Calgary (CA)
- Mayo Clinic (US)
- Sri Venkateshwara Hospital, Bangalore, India
- National Cancer Institute (UA)
- Queen Mary Hospital (CN)
- Unidade de Pesquisa em Oncologia Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Liver Unit, Hospital Universitario Central de Asturias, Universidad de Oviedo, Instituto Universitario de Oncología del Principado de Asturias–Obra Social Cajastur, Instituto de Investigación Sanitaria del Principado de Asturias, Fundación para la Investigación y la Innovación Biosanitaria del Principado de Asturia, Oviedo, Spain
- National Taiwan University (TW)
- 81th Hospital of PLA (CN)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- AstraZeneca (United States) (US)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- ORCID
- Lau, George
- Kudo, Masatoshi
- Chan, Stephen L.
- Kelley, Robin Kate
- Furuse, Junji
- Sukeepaisarnjaroen, Wattana
- Kang, Yoon-Koo
- Rimassa, Lorenza
- Breder, Valeriy
- Heurgué, Alexandra
- Tam, Vincent C.
- Mody, Kabir
- Yau, Thomas
- Cheng, Ann-Lii
- Qin, Shukui
- Galle, Peter R.
- Marcovitz, Michelle
- He, Philip
- Kurland, John F.
- Negro, Alejandra
- Sangro, Bruno
- Venue
- NEJM Evidence
- Publisher
- Massachusetts Medical Society
- Published
- 2022-07-26
- Volume
- 1
- Issue
- 8
- Pages
- EVIDoa2100070-EVIDoa2100070
- ISSN
- 2766-5526 (ISSN-L)
- OpenAlex
- W4281645619
- Cited by
- 1,576
- References
- 23
- Citations by year
- 2026: 356 · 2025: 450 · 2024: 421 · 2023: 284 · 2022: 63
- FWCI
- 181.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- NEJM Evidence (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Keywords
- tremelimumab, durvalumab, hepatocellular carcinoma, unresectable liver cancer, CTLA-4 blockade, PD-L1 blockade, sorafenib, overall survival, non-inferiority, immune checkpoint inhibitors, combination immunotherapy, progression-free survival, treatment-emergent adverse events, immune-related adverse events, non-small cell lung cancer
- MeSH terms
- Antineoplastic Agents, Immunological, Sorafenib, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Antibodies, Monoclonal, Humanized
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