Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

Background: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA.
Patients and Methods: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization).
Results: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified.
Conclusions: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.
Competing Interests: Disclosure BS reports consulting or advisory fees from AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Eisai, Incyte, IPSEN, Roche, Sirtex Medical, and Terumo; reports being an invited speaker for AstraZeneca, Bristol Myers Squibb, Eisai, Incyte, IPSEN, Roche, and Sirtex Medical; research funding (to institution) from Bristol Myers Squibb and Sirtex Medical; and reports being a steering committee member for AstraZeneca, Bristol Myers Squibb, Boston Scientific, and Roche. SLC reports advisory board fees from AstraZeneca, Eisai, and MSD; reports being an invited speaker for AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, IPSEN, MSD, and Roche; and research funding (to self) from Bayer, Eisai, IPSEN, MSD, and Sirtex Medical. RKK reports consulting or advisory fees from Agios, AstraZeneca, Exelixis, IPSEN, and MSD (to institution), and from Exact Sciences, IPSEN, Kinnate, Regeneron, and Tyra Biosciences (to self); and research funding (to institution) from Adaptimmune, Agios, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, EMD Serono, Exelixis, Genentech, Loxo Oncology, MSD, Novartis, Partner Therapeutics, QED, Relay Therapeutics, Roche Surface Oncology, and Taiho. GL reports consulting fees from AstraZeneca. MK reports being an invited speaker for Bayer, Chugai, Eisai, Eli Lilly, MSD, and Takeda; and research funding (to institution) from AbbVie, Chugai, EA Pharma, Eisai, GE HealthCare, Gilead Sciences, Otsuka, Sumitomo Dainippon Pharma, Taiho, and Takeda. MY reports grant/research funding (to institution) from Bristol Myers Squibb, Genentech, and Incyte; and consulting or advisory fees from AstraZeneca, Eisai, Exelixis, Genentech, Hepion, and Replimune. MY is a co-founder of Adventris Pharmaceuticals and holds equity. ENDT reports honoraria from Bristol Myers Squibb and Falk; consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Eli Lilly, IPSEN, Mallinckrodt, MSD, Pfizer, Roche, and Terumo; research funding from Arqule, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, IPSEN, and Roche; travel expenses from Arqule, AstraZeneca, Bayer, Bristol Myers Squibb, Celsion, and Roche; and is an employee of Boehringer Ingelheim. 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. YKK reports advisory board fees from ALX Oncology, Amgen, Blueprint, Bristol Myers Squibb, Daehwa, Marcrogenics, Merck, Novartis, Roche, Surface Oncology, and Zymeworks. PRG reports grant/research funding, and/or honoraria, from Adaptimmune, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Eisai, Eli Lilly, F. Hoffmann-La Roche, Guerbet, IPSEN, MSD, and Sirtex Medical. LR reports grant/research funding (to institution) from Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, IPSEN, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, and Zymeworks; consulting fees from 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, Eisai, Incyte, IPSEN, Merck Serono, Roche, and Servier; and travel expenses from AstraZeneca. AH reports consulting fees from AbbVie, AstraZeneca, Bayer, Intercept, and IPSEN. 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. TVD reports consulting fees from AstraZeneca, Bayer, Eisai, IPSEN, MSD, Novartis, Pfizer, Pierre Faber, Roche, and Taiho Pharmaceutical. SCT reports grant/research funding from AstraZeneca and Eisai; and consulting fees from AstraZeneca. VB reports advisory board fees from AstraZeneca, Bristol Myers Squibb, Eisai, F. Hoffman-La Roche, and Merck; reports 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. MR reports advisory board fees from AstraZeneca, Bayer, Bristol Myers Squibb, IPSEN, Lilly, Roche, and Universal DX; reports being an invited speaker for Bayer, Bristol Myers Squibb, BTG, Eisai, Gilead Sciences, Lilly, and Roche; and grant/research funding from Bayer and IPSEN. MM, MJP, CG, JFK, and AN are employees of and shareholders in AstraZeneca. GKAA 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. GKAA also reports filed patent PCT/US2014/031545, filed: 24 March 2014, and priority application Serial No.: 61/804,907, filed: 25 March 2013. All other authors have declared no conflicts of interest.
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