Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC
- PMID: 40222621
- DOI: 10.1016/j.jhep.2025.03.033
Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC
Abstract
Background & aims: In 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.
Methods: Participants 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.
Results: Median (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.
Conclusions: At 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.
Keywords: durvalumab; immune checkpoint inhibitor; overall survival; tremelimumab; unresectable HCC.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Conflict of interest LR reports grant/research funding (to institution) from AbbVie, Agios, AstraZeneca, BeiGene, Eisai, Eli Lilly, Exelixis, Fibrogen, Incyte, IPSEN, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, TransThera Sciences and Zymeworks; consulting fees from AbbVie, AstraZeneca, Basilea, Bayer, Bristol Myers Squibb, Eisai, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, IPSEN, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology and Zymeworks; honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, Guerbet, Incyte, IPSEN, Roche and Servier; and travel expenses from AstraZeneca and Servier. SLC reports advisory board fees from AstraZeneca, Eisai and MSD; being an invited speaker for AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Elevar, IPSEN, MSD and Roche; and research funding (to institution) from Bayer, Eisai, IPSEN, MSD and Sirtex Medical. BS reports consulting or advisory fees from AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Eisai, Incyte, Roche, Sirtex Medical and Terumo; being an invited speaker for AstraZeneca, Eisai, Incyte, Roche and Sirtex Medical; research funding (to institution) from Bristol Myers Squibb and Sirtex Medical; and being a steering committee member for AstraZeneca, Boston Scientific, Bristol Myers Squibb and Roche. GL reports being an invited speaker for AstraZeneca and BeiGene. MK reports being an invited speaker for Bayer, Chugai Pharma, Eisai, Eli Lilly, MSD and Takeda; and research funding (to institution) from AbbVie, Chugai Pharma, EA Pharma, Eisai, GE HealthCare, Gilead Sciences, Otsuka, Sumitomo Dainippon Pharma, Taiho and Takeda. MR reports advisory board fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Guerbet, IPSEN, Roche and Universal DX; being an invited speaker for Bayer, Bristol Myers Squibb, BTG, Eisai, Eli Lilly, Gilead Sciences and Roche; and grant/research funding (to institution) from Bayer and IPSEN. VB reports advisory board fees from AstraZeneca, Bristol Myers Squibb, Eisai, F. Hoffman-La Roche and Merck; being an invited speaker for Bristol Myers Squibb, Eisai, F. Hoffman-La Roche and Merck; and travel grants from Bayer Healthcare and F. Hoffman-La Roche. M-HR reports grant/contracts (to self) from AstraZeneca; consulting fees (to self) from Astellas, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, MSD and Ono Pharmaceutical; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (to self) from Astellas, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, MSD and Ono Pharmaceutical. YO has declared no conflicts of interest. WS has declared no conflicts of interest. MV reports consulting/advisory fees from AstraZeneca, Boston Scientific, Eisai-MSD and Roche; being an invited speaker for AstraZeneca, Boston Scientific, Eisai-MSD and Roche Molecular Diagnostics; and travel expenses from AstraZeneca, Eisai-MSD and Roche. DT reports advisory board fees from Amgen, AstraZeneca, Bristol Myers Squibb, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier and Takeda; and travel expenses from MSD, Pierre Fabre, Servier and Roche. OVC reports grant/contracts from Academic and Community Cancer Research United (ACCRU), Bristol Myers Squibb, Institut de Recherches Internationales Servier, National Cancer Institute, Syneos Health and Tempest Therapeutics; travel expenses from National Comprehensive Cancer Network; and participation on a data safety monitoring board or advisory board for National Comprehensive Cancer Network and Via Oncology Pathways. MB reports consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, ISPEN, MSD, Roche and Sirtex Medical; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Bayer, Eisai and Roche; and travel expenses from AstraZeneca, Bayer and Sirtex Medical. TVD reports consulting fees from AstraZeneca, Bayer, Eisai, IPSEN, MSD, Novartis, Pfizer, Pierre Fabre, Roche and Taiho Pharmaceutical. VCT reports grant/research funding (to institution) from AstraZeneca, Eisai, IPSEN and Roche; consulting fees from AstraZeneca and Incyte; and honoraria from AstraZeneca, Eisai, Incyte, IPSEN, Merck and Roche. AF reports being a principal investigator and invited speaker for AstraZeneca. JF reports grant/research funding from Astellas, Chugai Pharma, Daiichi Sankyo, Eisai, Incyte Japan, J-Pharma, Merck Bio, Mochida, MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Sanofi, Sumitomo Dainippon Bayer and Yakult Honsha; and consulting fees from Bayer, Chugai Pharma, Daiichi Sankyo, EA Pharma, Eisai, Eli Lilly Japan, Incyte Japan, Kyowa Hakko Kirin, Mylan EPD, MSD, Novartis, Ono Pharmaceutical, Pfizer, Sanofi, Servier Japan, Taiho Pharmaceutical, Takeda, Teijin Pharma and Yakult Honsha. L-BJ has declared no conflicts of interest. YKK reports advisory board fees from ALX Oncology, Amgen, Blueprint, Bristol Myers Squibb, Daehwa, MacroGenics, Merck, Novartis, Roche, Surface Oncology and Zymeworks. RKK reports consulting or advisory fees from Agios, AstraZeneca, and MSD (to institution), and from Elevar, GSK, Jazz Pharmaceuticals, J-Pharma, Moderna, Regeneron and Tyra Biosciences (to self); and research funding (to institution) from Agios, AstraZeneca, Bayer, Bristol Myers Squibb, Compass, Eli Lilly, EMD Serono, Exelixis, Genentech, Loxo Oncology, MSD, Novartis, Partner Therapeutics, QED, Relay Therapeutics, Roche, Servier, Surface Oncology, Taiho Pharmaceutical and Tyra Biosciences. MJP, DR, IX, JFK and AN are employees of and shareholders in AstraZeneca. GKA-A reports grant/research funding from Arcus, AstraZeneca, BioNtech, Bristol Myers Squibb, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed and Yiviva; and consulting fees from Adicet, Alnylam, AstraZeneca, Autem, BeiGene, Berry Genomics, Boehringer Ingelheim, Celgene, Cend, CytomX, Eisai, Eli Lilly, Exelixis, Flatiron, Genentech/Roche, Genoscience, Helio, Helsinn, Incyte, IPSEN, Merck, Nerviano, Newbridge, Novartis, QED, Redhill, Rafael, Servier, Silenseed, Sobi, Vector and Yiviva. GKA-A also reports filed patent PCT/US2014/031545, filed: 24 March 2014, and priority application Serial No.: 61/804,907, filed: 25 March 2013. Please refer to the accompanying ICMJE disclosure forms for further details.
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