Clinical Breakthrough: Five-Year Survival in Patients with Unresectable Hepatocellular Carcinoma Sets an Unprecedented Milestone Poised to Reshape Clinical Practice

A new exploratory analysis of the HIMALAYA phase III trial involving patients with unresectable hepatocellular carcinoma (uHCC, an advanced liver cancer that could not be treated with surgery or other localized treatments) has shown that one in five (19.6%) participants treated with STRIDE (Single Tremelimumab Regular Interval Durvalumab) a combination of two immunotherapies, remained alive after five years of follow-up versus one in 10 (9.4%) participants treated with sorafenib, a standard treatment for uHCC when the study was designed. The findings from the new exploratory analysis of the HIMALAYA study in the Journal of Hepatology, published by Elsevier, establish a new survival benchmark for people living with uHCC and may inform future treatment decisions by doctors and patients.

Advanced hepatocellular carcinoma (HCC) is a devastating disease that has historically carried a poor prognosis, with limited long-term survival largely due to late diagnosis and underlying advanced chronic liver disease. Previously reported results from the HIMALAYA study showed that participants treated with STRIDE lived longer than participants who received sorafenib. Now, findings from this exploratory analysis determined how long participants lived after five years of follow-up, and whether how long they lived was linked to changes in the size of their tumors after receiving treatment.

Lead investigator of the five-year analysis, Lorenza Rimassa, MD, Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy, notes, “Our finding that one in five participants treated with STRIDE is alive after five years represents a key clinical breakthrough in the advancement of treatment for uHCC. This remarkable five-year survival in a phase III trial was unimaginable only a few years ago and sets an unprecedented milestone that will inform clinical practice for years to come.”

Key Findings:

• HIMALAYA is the first phase III study to report five-year overall survival in uHCC.

• At five years, STRIDE sustained an overall survival benefit versus sorafenib and manageable safety – there were no new, late-onset serious side effects reported related to STRIDE.

• The overall survival rate at five years was 19.6% with STRIDE versus 9.4% with sorafenib, and participants who took durvalumab alone continued to live at least as long as those who took sorafenib.

• Overall survival with STRIDE was improved with disease control and any degree of tumor shrinkage, regardless of Response Evaluation Criteria in Solid Tumors (RECIST v1.1 response).

• Extended long-term overall survival with STRIDE occurred across all clinically relevant subgroups.

Author of an accompanying editorial, Pierre Nahon, MD, PhD, AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny; France, comments, “The most striking result of this analysis is that one in five patients treated with STRIDE remained alive after five years, a milestone that underscores the long-term potential of dual immunotherapy in uHCC. The findings of this study offer a new horizon of hope for patients and healthcare providers alike, reshaping clinical expectations and treatment goals in liver oncology.”

International coordinating investigator of the HIMALAYA trial, Ghassan K. Abou-Alfa, MD, JD, MBA, PhD, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Medical College, Cornell University, New York, New York; and Trinity College, Dublin, Ireland, concludes, “Overall survival is often discussed as a statistical endpoint in clinical trials, but for patients, it carries more personal meaning. Patients are often most concerned with their individual likelihood of living for a certain number of years, surviving to attend key milestones like a child’s graduation or travel to see the world while preserving their quality of life to enjoy time with loved ones. The findings we report in this long-term follow-up of the HIMALAYA study are worth celebrating and may help patients understand what these outcomes mean for them personally in terms of real time that may be gained.”

Notes for editors

The article is “Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC," by Lorenza Rimassa, Stephen L. Chan, Bruno Sangro, George Lau, Masatoshi Kudo, Maria Reig, Valeriy Breder, Min-Hee Ryu, Yuriy Ostapenko, Wattana Sukeepaisarnjaroen, Maria Varela, David Tougeron, Oxana V. Crysler, Mohamed Bouattour, Tu Van Dao, Vincent C. Tam, Adilson Faccio, Junji Furuse, Long-Bin Jeng, Yoon Koo Kang, Robin K. Kelley, Michael J. Paskow, Di Ran, Ioannis Xynos, John F. Kurland, Alejandra Negro, and Ghassan K. Abou-Alfa (https://doi.org/10.1016/j.jhep.2025.03.033).

The article is openly available at https://www.journal-of-hepatology.eu/article/S0168-8278(25)00226-0/fulltext.

Clinical trial number: NCT03298451.

Journalists wishing to interview the authors should contact Lorenza Rimassa, MD, at [email protected].

This study was sponsored by AstraZeneca. The funder of the study had a role in study design, data analysis, data interpretation, and writing of the report. The sites entered the data; the funders had clinical research associates and monitors to liaise with the study.

The editorial commentary is "Establishing five-year overall survival as a new standard for trials in advanced HCC," by Pierre Nahon (https://doi.org/10.1016/j.jhep.2025.05.001).

The article is openly available for 60 days at https://www.journal-of-hepatology.eu/article/S0168-8278(25)02199-3/fulltext.

Journalists wishing to reach Pierre Nahon, MD, PhD, for comment should contact him at [email protected].

Full text of these articles is also available to credentialed journalists upon request; contact Freya Weise at +33 (1) 71 16 55 00 or [email protected].

Both articles appear online in advance of the Journal of Hepatology, volume 83, issue 4 (October 2025) published by Elsevier.

About the Journal of Hepatology

The Journal of Hepatology, the premier journal devoted to liver diseases, is the official journal of the European Association for the Study of the Liver (EASL). It publishes original papers, reviews, case reports, and letters to the Editor concerned with clinical and basic research in the field of hepatology. The journal has a 2024 Impact Factor of 33 (Source: Journal Citation Reports™ from Clarivate, 2025). www.journal-of-hepatology.eu

About EASL

In the fifty plus years since EASL was founded, it has grown from a small organization that played host to 70 participants at its first meeting, to becoming the leading international liver association. EASL attracts the foremost hepatology experts as members and has an impressive track record in promoting research in liver disease, supporting wider education, and promoting changes in European liver policy. www.easl.eu

About Elsevier

Elsevier is a global leader in advanced information and decision support. For over a century, we have been helping advance science and healthcare to advance human progress. We support academic and corporate research communities, doctors, nurses, future healthcare professionals and educators across 170 countries in their vital work. We do this by delivering mission-critical insights and innovative solutions that combine trusted, evidence-based scientific and medical content with cutting-edge AI technologies to help impact makers achieve better outcomes. We champion inclusion and sustainability by embedding these values into our products and culture, working with the communities that we serve. The Elsevier Foundation supports research and health partnerships around the world.

Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers. For more information, visit www.elsevier.com and follow us on social media @ElsevierConnect.