Evidence map›Paper›PMID 40222621›Full record

Trial reportJournal of hepatology2025

Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC.

Lorenza Rimassa, Stephen L Chan, Bruno Sangro, George Lau, Masatoshi Kudo, Maria Reig, Valeriy Breder, Min-Hee Ryu, Yuriy Ostapenko, Wattana Sukeepaisarnjaroen and 17 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase III
PubMed Publisher
In one paragraph

Trial report in Journal of hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03298451 (A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma), which is not on this map. Cited by 98 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03298451 phase3active not recruitingnot on this map

A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

TypeinterventionalSponsorAstraZenecaRan2017 to 2027Enrolled1,324ConditionsHepatocellular CarcinomaArmsDurvalumab, Tremelimumab (Regimen 1), Tremelimumab (Regimen 2), Sorafenib, Durvalumab (Regimen 1)
3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Review
  6. Stratifying Cardiovascular Risk in Patients With HCC Receiving Atezolizumab/Bevacizumab: A Comparison of ESC and CARDIOSOR Scores.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
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  20. Baseline DCP May Modify Response to Atezolizumab-Bevacizumab Versus Durvalumab-Tremelimumab in Unresectable HCC.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article

38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Lorenza RimassaDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. Electronic address: lorenza.rimassa@hunimed.eu.
Stephen L ChanState 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 of China.
Bruno SangroLiver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona - Madrid, Spain.
George LauHumanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong Special Administrative Region of China.
Masatoshi KudoDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
Maria ReigBarcelona Clinic Liver Cancer (BCLC), Liver Unit, Hospital Clinic de Barcelona, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain.
Valeriy BrederDepartment of Chemotherapy, N. N. Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation.
Min-Hee RyuDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Yuriy OstapenkoDepartment of Minimally Invasive and Endoscopic Surgery, Interventional Radiology, National Cancer Institute, Kyiv, Ukraine.
Wattana SukeepaisarnjaroenDepartment of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand.
Maria VarelaLiver Unit, Hospital Universitario Central de Asturias, IUOPA, ISPA, FINBA, Universidad de Oviedo, Oviedo, Spain.
David TougeronDepartment of Gastroenterology and Hepatology, Poitiers University Hospital, Poitiers, France.
Oxana V CryslerRogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.
Mohamed BouattourLiver Cancer Unit, AP-HP Hôpital Beaujon, Paris, France.
Tu Van DaoCancer Research and Clinical Trials Center, Department of Optimal Therapy, National Cancer Hospital, Hanoi, Vietnam.
Vincent C TamDepartment of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
Adilson FaccioDepartment of Oncology, CEON - Centro Especializado em Oncologia, Ribeirao Preto, Brazil.
Junji FuruseDepartment of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
Long-Bin JengDepartment of Surgery, China Medical University and Hospital, Taichung, Taiwan, Republic of China.
Yoon Koo KangDepartment of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Robin K KelleyHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
Michael J PaskowGlobal Medical Affairs, AstraZeneca, Gaithersburg, Maryland, USA.
Di RanStatistics, AstraZeneca, Gaithersburg, Maryland, USA.
Ioannis XynosOncology R&D, Late-Stage Development, AstraZeneca, Cambridge, UK.
John F KurlandOncology R&D, Late-Stage Development, AstraZeneca, Gaithersburg, Maryland, USA.
Alejandra NegroOncology R&D, Late-Stage Development, AstraZeneca, Gaithersburg, Maryland, USA.
Ghassan K Abou-AlfaDepartment of Medicine, Memorial Sloan Kettering Cancer Center, Cornell University, New York, New York, USA; Weill Medical College, Cornell University, New York, New York, USA; Trinity College Dublin, Dublin, Ireland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsIn the phase III HIMALAYA study (NCT03298451), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) vs. sorafenib in unresectable HCC and demonstrated long-term survival benefits. We report an updated exploratory analysis of OS after 5 years of follow-up, including survival by multiple tumour response measures.

methodsParticipants were randomised to STRIDE (tremelimumab plus durvalumab), durvalumab or sorafenib. OS, depth of response and serious adverse events were assessed. Extended long-term survivors (≥48 months beyond randomisation) were described. The updated data cut-off was 01 March 2024.

resultsMedian (95% CI) follow-up durations were 62.49 (59.47-64.79) months (STRIDE) and 59.86 (58.32-61.54) months (sorafenib). The OS hazard ratio (95% CI) for STRIDE vs. sorafenib was 0.76 (0.65-0.89). OS rates at 60 months for STRIDE vs. sorafenib were 19.6% vs. 9.4% overall, 28.7% vs. 12.7% in participants achieving disease control per RECIST v1.1, and 50.7% vs. 26.3% in participants achieving >25% tumour shrinkage. No late-onset treatment-related serious adverse events were reported for STRIDE. There were more extended long-term survivors with STRIDE (83/393, 21.1%) than sorafenib (45/389, 11.6%), and extended long-term survival occurred across all clinically relevant subgroups.

conclusionsAt 5 years, STRIDE sustained an OS benefit vs. sorafenib and maintained a manageable safety profile. OS benefit with STRIDE was improved in participants with disease control. Data suggest that any degree of tumour shrinkage with STRIDE can be associated with improved OS, indicating that conventional response measures may not fully capture the benefits of STRIDE. Nevertheless, participants experiencing deep responses appear to have the greatest benefit. STRIDE continues to set new benchmarks in unresectable HCC with 1 in 5 patients alive at 5 years. CLINICAL TRIAL NUMBER: NCT03298451. IMPACT AND IMPLICATIONS: The phase III HIMALAYA study showed that STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) vs. sorafenib in participants with unresectable HCC, including after 4 years of follow-up. Understanding the efficacy and safety of STRIDE over the longer term is important for healthcare providers; here, we demonstrate that STRIDE sustained an OS benefit vs. sorafenib and maintained a manageable safety profile after 5 years of follow-up. OS benefit with STRIDE was improved in participants with disease control and any degree of tumour shrinkage, indicating that conventional response measures may not fully capture the benefits of STRIDE. These findings are important as they set new benchmarks in unresectable HCC and may help guide clinical decisions in the future.

Indexed as

Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, HepatocellularLiver NeoplasmsAgedFemaleFollow-Up StudiesHumansMaleMiddle AgedSorafenibSurvival RateAntibodies, MonoclonalAntibodies, Monoclonal, HumanizeddurvalumabSorafenibtremelimumabdurvalumabimmune checkpoint inhibitoroverall survivaltremelimumabunresectable HCC

Identifiers

PMID40222621

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.