The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
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.)
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“In HIMALAYA, durvalumab plus tremelimumab yielded an objective response rate of 20% and median duration of response of 22•3 months.7”
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21492 · Cited by 84,109
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534
Aaronson, N. K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N. J., Filiberti, A., Flechtner, H., Fleishman, S. B., Haes, J. C. J. M. D., et al. (1993) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/85.5.365 · Cited by 16,005
Sorafenib in advanced hepatocellular carcinoma
Llovet, J. M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.-F., de Oliveira, A. C., Santoro, A., Raoul, J.-L., Forner, A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708857 · Cited by 13,097
Self-citationEASL Clinical Practice Guidelines: Management of hepatocellular carcinoma
Galle, P. R., Forner, A., Llovet, J. M., Mazzaferro, V., Piscaglia, F., Raoul, J.-L., Schirmacher, P., & Vilgrain, V. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.03.019 · Cited by 11,406
Self-citationCombined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma
Finn, R. S., Qin, S., Ikeda, M., Galle, P. R., Ducreux, M., Kim, T.-Y., Kudo, M., Breder, V., Merle, P., Kaseb, A. O., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1915745 · Cited by 7,470
Self-citationOncology meets immunology: the cancer-immunity cycle.
Chen, D. S., & Mellman, I. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.012 · Cited by 6,929
Kudo, M., Finn, R. S., Qin, S., Han, K.-H., Ikeda, K., Piscaglia, F., Baron, A., Park, J.-W., Han, G., Jassem, J., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30207-1 · Cited by 5,497
Self-citationSchadendorf, D., Hodi, F. S., Robert, C., Weber, J. S., Margolin, K., Hamid, O., Patt, D., Chen, T.-T., Berman, D. M., & Wolchok, J. D. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.56.2736 · Cited by 2,141
Cited by
Sorted by citations
Items 901–1,000 of 1,001
Sato, R., Suzuki, T., Matsuura, K., Kato, D., Hayashi, K., Okayama, K., Okumura, F., Sobue, S., Kusakabe, A., Hasegawa, I., et al. (2025) · Hepatology Research · doi:10.1111/hepr.70101 · Cited by 2
Yang, J., Xu, Q., & Wu, S. (2025) · Medicine · doi:10.1097/md.0000000000046799 · Cited by 2
“In advanced HCC, The triple therapy demonstrated superior ORR and PFS compared to previous studies involving atezolizumab plus bevacizumab, [14] sintilimab plus bevacizumab biosimilar, [15] camrelizumab–rivo-ceranib, [27] tremelimumab plus durvalumab, [11] and other TKI therapies.”
Ye, K., Zhou, J., Lin, J., Li, Y., Luo, Y., & Xie, F. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1707622 · Cited by 3
“Relevant randomized controlled trials demonstrate that sorafenib and regorafenib exhibit favorable single-agent ef fi cacy and safety pro fi les in patients with advanced hepatocellular carcinoma (14 – 16).”
Immunometabolic heterogeneity in hepatocellular carcinoma: Transforming cold tumors into hot tumors
Xu, Y., & Sun, J. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105123 · Cited by 2
Next-generation therapies for hepatocellular carcinoma: CAR-T cell and anticancer peptide synergy
Kannan, H. T., & Pan, I. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.150512 · Cited by 2
Hepatocellular Carcinoma – from Immunobiology to Immunotherapy
Roehlen, N., Bengsch, B., Rennert, C., Schultheiß, M., & Thimme, R. (2026) · Zeitschrift für Gastroenterologie · doi:10.1055/a-2722-5684 · Cited by 2
“Factors influencing the tumor immune microenvironment include the tumor mutational profile [22] or the underlying the role of innate and adaptive immune cells”
Li, M., Song, W., Wu, Y., Lin, H., Liu, W., & Chi, J. (2026) · Hepatoma Research · doi:10.20517/2394-5079.2025.57 · Cited by 2
Li, H.-L., Zhou, H., Zhang, Y.-Y., Lai, J.-T., Zhou, Z.-Z., Huang, J.-Y., Guo, S., Wang, Y. F., Huang, W.-J., & Tian, X.-P. (2026) · Science China Life Sciences · doi:10.1007/s11427-025-3093-8 · Cited by 2
Advancing systemic therapy for biliary tract cancer: current strategies and emerging paradigms
Choucair, K., Chamseddine, S., Azmi, A. S., & Philip, P. A. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1769447 · Cited by 2
“Following the success of ICIs in gastrointestinal tumors, including hepatocellular carcinoma (148), their use in BTCs has been extensively evaluated.”
Guo, J., Bhela, S., Sharma, M., Protti, G., Luoh, S.-M., Wang, S., Firmino, N. S., Dasoveanu, D., Chan, C. K., Ibarra-Lopez, V., et al. (2026) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-25-0836 · Cited by 2
Chimeric antigen receptor therapy for hepatocellular carcinoma
Kocheise, L., Benmebarek, M.-R., Ho, M., & Greten, T. F. (2026) · Seminars in Immunology · doi:10.1016/j.smim.2025.102000 · Cited by 2
Hazari, M. W. A. D., Nandi, S., & Das, C. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153656 · Cited by 3
Nishio, A., Kodama, T., Daiku, K., Maesaka, K., Tanaka, S., Nozaki, Y., Kurahashi, T., Matsumoto, K., Nawa, T., Tawara, S., et al. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-013648 · Cited by 2
Nakamura, D., Nishio, T., Oguma, Y., Taura, K., Koyama, Y., Zhan, M., Kurata, Y., Okura, K., Yoh, T., Nishino, H., et al. (2026) · Hepatology Communications · doi:10.1097/hc9.0000000000000930 · Cited by 2
Lee, P.-C., Cortellini, A., Stefanini, B., Yoo, C., Chon, H. J., Cheon, J., Kudo, M., Nishida, N., Scheiner, B., Pinter, M., et al. (2026) · European Journal of Cancer · doi:10.1016/j.ejca.2026.116749 · Cited by 2
Self-citationBiologically Refined Oncological Resectability for Hepatocellular Carcinoma
Aso, K., Takeda, Y., Takahashi, A., Irie, S., Hirata, Y., Ichida, H., Yoshioka, R., Kotera, Y., Mise, Y., & Saiura, A. (2026) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.70119 · Cited by 2
“In contrast, recent systemic therapies, including tyrosine kinase inhibitors and programmed death-1 inhibitors, have demonstrated higher response rates of 20%–36% in patients with unresectable HCC [16, 17], and surgery following such therapies has resulted in favorable long-term outcomes [18].”
Agrawal, D., Jothimani, D. K., Bhoori, S., Reddy, G. N., Saigal, S., Rela, M., & Mazzaferro, V. (2026) · Hepatology International · doi:10.1007/s12072-026-11097-1 · Cited by 2
Dalbeni, A., Vicardi, M., Stefanini, B., Cinque, F., Cespiati, A., Cattazzo, F., Ravaioli, F., Mantovani, A., & Lombardi, R. (2026) · Digestive and Liver Disease · doi:10.1016/j.dld.2026.04.013 · Cited by 2
Park, C., Wong, T. L., & K, S. (2026) · Carcinogenesis · doi:10.1093/carcin/bgag040 · Cited by 3
“Combination therapies, such as atezolizumab + bevacizumab in IMbrave150 [121], trem-elimumab + durvalumab in HIMALAYA [122], and pembrolizumab + lenvatinib in LEAP-002 [123], have shown promising results in improving OS and quality of care, transforming the treatment approach for patients with…”
Odent, A. V., Campani, C., Bouattour, M., Touchefeu, Y., Delhoume, V., Rosmorduc, O., Pascale, A., An, J., Lee, H. C., Regnault, H., et al. (2026) · JHEP Reports · doi:10.1016/j.jhepr.2026.101915 · Cited by 2
Fu, Y., Ge, Y., Yi, S., Peng, Q., Jiang, H., & Zhou, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1854700 · Cited by 2
van den Broecke, L., der Vreken, A. V., Watté, F., Meeus, F., Veirman, K. D., Breckpot, K., Bruyne, E. D., & Menu, E. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02923-x · Cited by 3
“201 In contrast, CTLA-4 monotherapy has limited ef fi cacy in most epithelial cancers, likely due to insuf fi cient tumour immunogenicity, despite high mutational burdens, or dominant peripheral suppression.”
Current Immune Checkpoint Inhibitor Genetic Biomarker Exploration in Gastrointestinal Tumors
Rogers, J. E., Yamashita, K., Sewastjanow‐Silva, M., & Ajani, J. A. (2022) · Cancers · doi:10.3390/cancers14194804 · Cited by 2
“MSI-H/dMMR is also associated with other GI tumors at a lower incidence (i.e., ~2–2.5% pancreatic; ~2% biliary; ~2% gallbladder, etc.) and even more rarely seen in some (Hepatocellular carcinoma (HCC) and anal cancer given different cancer etiologies) [22–24].”
BackgroundInfluentialDai, M., Lui, R. N.-S., & Lau, L. H. S. (2023) · Hepatoma Research · doi:10.20517/2394-5079.2023.33 · Cited by 2
BMJ Publishing Group Ltd (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002794add1 · Cited by 2
Management of Hepatocellular Carcinoma: The East-West Difference
Feng, Y., & Chan, S. L. (2023) · Current Chinese Science · doi:10.2174/2210298103666230912143208 · Cited by 2
Self-citationClinical Updates for Gastrointestinal Malignancies
Laface, C., & Memeo, R. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13091424 · Cited by 2
Current updates in HCC screening and treatment
Hunold, T. M., & Pillai, A. A. (2023) · Clinical Liver Disease · doi:10.1097/cld.0000000000000083 · Cited by 2
Gao, H., Chang, R.-Z., Chen, X., Zhang, W., Zhang, B., Luo, X., & Ding, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1274449 · Cited by 2
Yamamoto, M., Terashima, T., Yamashita, T., Seki, A., Nakagawa, H., Nio, K., Shimakami, T., Takatori, H., Arai, K., Mizukoshi, E., et al. (2023) · Hepatology Research · doi:10.1111/hepr.13975 · Cited by 2
Osuga, T., Miyanishi, K., Itô, R., Tanaka, S., Kubo, T., Hamaguchi, K., Ohnuma, H., Murase, K., Takada, K., Yamamoto, M., et al. (2023) · Kanzo · doi:10.2957/kanzo.64.559 · Cited by 2
Stem Cell Origin of Cancer: Clinical Implications for Cancer Immunity and Immunotherapy
Tu, S., Aydın, A. M., Maraboyina, S., Chen, Z., Singh, S. R. K., Gökden, N., & Langford, T. (2023) · Cancers · doi:10.3390/cancers15225385 · Cited by 2
Focal Hepatocellular Carcinoma in Pancreas
Ahmed, Y. A., Sakhawat, U., Malik, F., Haleema, S., Chin, D., & Marhaba, A. (2024) · Journal of Medical Cases · doi:10.14740/jmc4181 · Cited by 2
Abou‐Alfa, G. K., Geyer, S. M., Nixon, A. B., Innocenti, F., Shi, Q., Kumthekar, P., Jacobson, S. B., Dika, I. E., Yaqubie, A., Lopez, J., et al. (2024) · Cancer Research Communications · doi:10.1158/2767-9764.crc-22-0516 · Cited by 2
Self-citationHämatologische Neoplasien und solide Tumore
Ludwig, W.-D., Ganser, A., & Maschmeyer, G. (2023) · Springer eBooks · doi:10.1007/978-3-662-68371-2_5 · Cited by 2
Multidisciplinary Care and Multimodal Treatment Approaches for Unresectable Hepatocellular Carcinoma
Lang, D., Agarwal, R., Brown, S. A., Borgmann, A. J., Lockney, N. A., Goff, L. W., & Heumann, T. R. (2024) · Advances in Oncology · doi:10.1016/j.yao.2024.02.002 · Cited by 2
Chamseddine, S., LaPelusa, M. B., Xiao, L., Mohamed, Y. I., Lee, S., Hu, Z., Hatia, R. I., Hassan, M. M., Yao, J. C., Duda, D. G., et al. (2024) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s452564 · Cited by 2
“8 While both atezolizumab plus bevacizumab and durvalumab plus tremelimumab (D+T) are approved by the Food and Drug Administration (FDA) in the first-line setting for patients with advanced HCC, these regimens have relatively different side effect profiles.”
BackgroundMajeed, A., Alaparthi, S. S., Halegoua-DeMarzio, D. L., Eberle-Singh, J. A., Jiang, W., Anne, P. R., Shah, A. P., Bowne, W. B., & Lin, D. (2024) · World Journal of Oncology · doi:10.14740/wjon1840 · Cited by 2
“Though generally well tolerated, 50.5% of patients experienced treatment-related grade 3 or 4 adverse events, with 20.1% of patients experiencing immune-mediated adverse events requiring high dose steroids [20].”
BackgroundInfluentialCastria, T. B. D., & Kim, R. D. (2024) · Pragmatic and Observational Research · doi:10.2147/por.s395974 · Cited by 2
Review of immune therapy in HCC: Where are we now and what is the future?
Zanuso, V., Pirozzi, A., Tesini, G., & Rimassa, L. (2024) · Clinical Liver Disease · doi:10.1097/cld.0000000000000149 · Cited by 2
Self-citationWang, Y., Lau, W. Y., Li, Y., Tian, Y., Lei, Y., Feng, X., & Wang, J. (2024) · PLoS ONE · doi:10.1371/journal.pone.0306869 · Cited by 2
Impact of neoadjuvant multimodal therapy in the setting of locally advanced hepatocellular carcinoma
Ferraro, D., Falaschi, F., Nazzaro, L., & Vennarecci, G. (2024) · World Journal of Gastroenterology · doi:10.3748/wjg.v30.i28.3452 · Cited by 2
Liu, L., He, W., & Liu, J. (2024) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2024.102465 · Cited by 2
Shin, Y. S., Yun, J. K., Jung, J., Park, J., Song, S. Y., Choi, E. K., Choi, S., Kim, H. R., Kim, Y., Kim, D. K., et al. (2024) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2024.09.022 · Cited by 2
Liu, Y., Ji, H., Wu, L., Wang, X.-X., Yang, Y., Zhang, Q., & Zhang, H. (2024) · Molecular Therapy Oncology · doi:10.1016/j.omton.2024.200890 · Cited by 2
Li, S., Mei, J., Zhao, R., Zhou, J., Wang, Q., Lu, L., Li, J., Zheng, L., Wei, W., & Guo, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1491857 · Cited by 2
“In the phase III HIMALAYA study uHCC, STRIDE (Single Tremelimumab Regular Interval Durvalumab) signi fi cantly improved overall survival (OS) versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib for OS (7).”
BackgroundSystemic Therapy for Hepatocellular Carcinoma
Kinsey, E. N., & Morse, M. A. (2024) · Clinics in Liver Disease · doi:10.1016/j.cld.2024.08.010 · Cited by 4
Chansangrat, J., & Gadani, S. (2024) · Hepatoma Research · doi:10.20517/2394-5079.2024.92 · Cited by 2
Tian, J., Pan, S., Wang, Y., Yu, Y., Wang, S., Shen, Y., Yang, L., Liu, X., Qiu, Q., Luan, J., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12122769 · Cited by 2
Ghammem, N., Bischoff, H., Chiappa, P., Somme, L., & Moinard‐Butot, F. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1487227 · Cited by 2
Mendes, J. L., Spencer, A. S., Pimentel, J. C., Sardinha, M., Ferreira, J. B., & da Luz, R. (2024) · GE Portuguese Journal of Gastroenterology · doi:10.1159/000543288 · Cited by 2
“Moreover, long-term survival bene fi ts, often captured in early plateau survival curves among IO-treated populations, are less clear in HCC trials [7, 13, 14].”
InfluentialWei, M., Zhang, P., Yang, C. F., & Li, Y. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1500496 · Cited by 2
“Furthermore, the antitumor effects of these inhibitors as monotherapies are often unsatisfactory (11).”
Wang, X., Huang, J., Liu, Y., Wu, L., Cai, R., Zheng, Q., & Li, L. (2024) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-024-03797-0 · Cited by 2
Daiku, K., Nishio, A., Hikita, H., Doi, A., Hayashi, K., Kato, S., Sasaki, Y., Shimoda, A., Kudo, S., Fukumoto, K., et al. (2025) · Gastro Hep Advances · doi:10.1016/j.gastha.2025.100634 · Cited by 2
Miwa, C., Ogasawara, S., Yonemoto, T., Yumita, S., Okubo, T., Nakagawa, M., Koroki, K., Inoue, M., Kanogawa, N., Nakamura, M., et al. (2025) · Cancer Medicine · doi:10.1002/cam4.70642 · Cited by 2
Sangro, B., & Argemí, J. (2025) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-025-01009-x · Cited by 2
“…once again, as happened with the three pivotal trials that switched the standard of care for advanced-stage HCC from tyrosine-kinase inhibitors to ICI-containing regimens 1–3 , how rationally designed combinations that target complementary immune signalling pathways can improve patient outcomes.”
Self-citationZhou, Q., Li, H., Ye, L., Li, R., Wang, X., Wang, W., Liu, M., Duan, F., & Huang, Z. (2025) · La radiologia medica · doi:10.1007/s11547-025-01975-3 · Cited by 2
Tang, P., & Zhou, F. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1535444 · Cited by 2
Suzuki, T., Narita, K., Matsuura, K., Kato, D., Hayashi, K., Okayama, K., Okumura, F., Sobue, S., Kusakabe, A., Hasegawa, I., et al. (2025) · Oncology · doi:10.1159/000544051 · Cited by 2
Li, X., Qin, Z., Chen, H., Chen, D., Alimu, N., Li, D., Cheng, X., Yan, Q., Zhang, L., Liu, X., et al. (2025) · International Journal of Immunopathology and Pharmacology · doi:10.1177/03946320251333975 · Cited by 2
Brown, T. J., Amit, U., Gheewala, R., Ben‐Josef, E., & Karasic, T. B. (2025) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000001214 · Cited by 2
Liver transplantation for hepatocellular carcinoma following immunotherapy
Marino, R., Hassan, A. T., Fagenson, A. M., & Tabrizian, P. (2025) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000001228 · Cited by 2
Nivolumab plus ipilimumab in hepatocellular carcinoma
Vithayathil, M. K., & Sharma, R. (2025) · The Lancet · doi:10.1016/s0140-6736(25)00417-9 · Cited by 2
Wu, D., Liu, N., Dong, H., Zhou, K., Du, L., Li, Y., Yanjun, C., & Fu-ping, M. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1504917 · Cited by 2
Adhikari, S., & Doolin, J. W. (2025) · Case Reports in Oncology · doi:10.1159/000546711 · Cited by 2
“Immunotherapy has revolutionized treatment, offering superior survival benefits compared to sorafenib, as demonstrated by trials like IM-brave150 and HIMALAYA [2, 3].”
InfluentialDiscovery and Validation of Non-canonical Antigens for Hepatocellular Carcinoma Immunotherapy
Li, S., Dong, Y., Liu, J., Li, S., Pu, D., Guo, Y., Wong, C. K., Wong, N., & Wong, J. W. H. (2026) · Genomics Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzag082 · Cited by 2
Matono, T., Tada, T., Kumada, T., Hiraoka, A., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., et al. (2025) · Liver International · doi:10.1111/liv.70217 · Cited by 2
“More recently, in 2023, durvalumab in combination with tremelimumab was introduced as an initial immunotherapeutic regimen based on the findings of the HIMALAYA trial, further expanding first-line systemic treatment options for HCC [8].”
Self-citationRouge, T. D. L. M., Frenel, J., Cropet, C., Borcoman, É., Hervieu, A., Emile, G., Augereau, P., Charafe‐Jauffret, E., Legrand, F., Dassé, E., et al. (2025) · The Breast · doi:10.1016/j.breast.2025.104549 · Cited by 2
“For instance, a single dose of the anti-CTLA-4 trem-elimumab (Treme) with anti-PD-L1 durvalumab (Durva) improved OS compared to sorafenib in systemic treatment-naive patient with unresectable HCC [7].”
Ohama, H., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., Fukunishi, S., et al. (2025) · Journal of Gastroenterology · doi:10.1007/s00535-025-02290-4 · Cited by 2
Self-citationChou, T., Wu, C.-F., Lin, C., & Hsu, C. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1624908 · Cited by 2
“However, evidence their use in patients with Vp4 invasion remains limited, as these patients were speci fi cally excluded from the pivotal REFLECT and HIMALAYA trials (21, 22).”
Niitsu, H., Makishima, H., Hasegawa, N., Ikeda, T., Iizumi, T., SAITO, T. K., Numajiri, H., Nakai, K., Mizumoto, M., Okumura, T., et al. (2025) · Liver Cancer · doi:10.1159/000548347 · Cited by 2
“The recent introduction of immune checkpoint inhibitors has significantly improved the prognosis for patients with unresectable HCC [24–27].”
Akyıldız, A., Yavuz, B. G., İsmayılov, R., Büyükaksoy, M., Sözen, E. S., Eid, J. R., Avritscher, R., Lee, S. S., Yalçın, Ş., & Kaseb, A. O. (2025) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-025-01306-9 · Cited by 3
“Despite the encouraging PFS benefit, the OS gain was modest compared with the survival outcomes achieved with modern systemic regimens such as atezolizumab–bevacizumab [43] or dur-valumab–tremelimumab [44].”
Myocarditis induced by durvalumab in a patient with hepatocellular carcinoma: A case report
Alfehaid, L., Alsuhebany, N., AlDoughaim, M., Bukhari, R., Sait, W. A., Alshammari, K. M., & Aziz, M. (2025) · Saudi Pharmaceutical Journal · doi:10.1007/s44446-025-00041-3 · Cited by 3
Practice-Changing Evidence in Surgical Oncology 2021: Hepatobiliary Articles
Wei, A. C.-C. (2023) · Annals of Surgical Oncology · doi:10.1245/s10434-023-13132-z · Cited by 2
Immuntherapie in der Hepatogastroenterologie: Wirkung und Nebenwirkung
Krimmel, L., Quante, M., & Bengsch, B. (2023) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-1919-8494 · Cited by 2
“Entität ICI-Therapie Ösophagus Plattenepithelkarzinom ▪ Adjuvante Therapie mit Nivolumab bei vorheriger Radiochemotherapie und ypT+ oder ypN+ [1] ▪ Nivolumab + CTx oder Nivolumab + Ipilimumab als palliative Erstlinientherapie, wenn TPS > 1% ▪ Pembrolizumab + CTx als palliative Erstlinientherapie, wenn CPS> 10 ▪ Nivolu…”
BackgroundInfluentialTaouli, B. A., Ba‐Ssalamah, A., Chapiro, J., Chhatwal, J., Fowler, K. J., Kang, T. W., Knobloch, G., Koh, D., Kudo, M., Lee, J. M., et al. (2023) · European Radiology · doi:10.1007/s00330-023-09919-z · Cited by 2
Self-citationINASL Consensus on Management of HCC: Navigating an Evolving Field
Singal, A. G., Pillai, A. A., & Parikh, N. D. (2023) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2023.10.003 · Cited by 2
Update on systemic therapy for hepatocellular carcinoma
Ikeda, M., Shibuki, T., Taira, T., Inoue, K., Yamaguchi, S., & Fukushi, K. (2023) · Kanzo · doi:10.2957/kanzo.64.540 · Cited by 2
Safety and Efficacy of Lenvatinib in Very Old Patients with Unresectable Hepatocellular Carcinoma
Camera, S., Rimini, M., Rossari, F., Tada, T., Suda, G., Shimose, S., Kudo, M., Yoo, C., Cheon, J., Finkelmeier, F., et al. (2024) · Targeted Oncology · doi:10.1007/s11523-023-01029-6 · Cited by 2
“More recently, the phase III HIMALAYA trial showed that durvalumab with a single, high priming dose of treme-limumab (STRIDE regimen), can significantly improve OS versus sorafenib as a first-line treatment (16.4 months versus 13.8 months; HR 0.78) [7].”
InfluentialSelf-citationTu, S., Trikannad, A. K., Vellanki, S., Hussain, M., Malik, N., Singh, S. R. K., Jillella, A., Obulareddy, S. J., Malapati, S. J., Bhatti, S. A., et al. (2024) · Cancers · doi:10.3390/cancers16061151 · Cited by 3
“Similarly, tremelimumab + durvalumab showed superiority over sorafenib; however, whether it is superior to durvalumab alone is less evident in the HIMALAYA trial [63].”
BackgroundWonglhow, J., Sunpaweravong, P., Sathitruangsak, C., & Dechaphunkul, A. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14040403 · Cited by 2
Evolution of systemic therapy for advanced-stage hepatocellular carcinoma
Hur, M. H., & Kim, Y. J. (2022) · HepatoBiliary Surgery and Nutrition · doi:10.21037/hbsn-22-507 · Cited by 2
“Especially, efficacy of durvalumab plus tremelimumab (durva-treme) was proven in the HIMALAYA trial, the first successful combination of PD-L1 and CTLA-4 antagonists (14).”
Approach to systemic therapy in advanced hepatocellular carcinoma
Sankar, K. N., Gong, J., Kosari, K., Nissen, N. N., & Yang, J. D. (2022) · HepatoBiliary Surgery and Nutrition · doi:10.21037/hbsn-22-530 · Cited by 1
“Further, durvalumab monotherapy was non-inferior to sorafenib (6).”
Guidelines for hepatobiliary cancers: treatment strategies in the East and West
Midorikawa, Y. (2023) · HepatoBiliary Surgery and Nutrition · doi:10.21037/hbsn-23-225 · Cited by 2
“In addition to Atezo-Bev, combined durvalumab and tremelimumab is also the first-line treatment based on data from the phase III HIMALAYA trial (12) in BCLC.”
ESR Bridges: imaging and treatment of hepatocellular carcinoma—a multidisciplinary view
Bouattour, M., Vilgrain, V., & Sepulveda, A. (2024) · European Radiology · doi:10.1007/s00330-023-10579-2 · Cited by 2
Maximizing therapeutic outcomes in hepatocellular carcinoma: Insights into combinatorial strategies
İlhan, Y., & Ergün, Y. (2024) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v16.i7.2888 · Cited by 2
“Therefore, making advanced interpretations regarding the effectiveness and safety of TACE in these randomized studies is not feasible[25,26].”
Abdelrahim, M., & Esmail, A. (2025) · Immunotherapy · doi:10.1080/1750743x.2025.2539064 · Cited by 2
Hargrave, D., Marshall, L. V., André, N., Krystal, J., Ladle, B. H., Robbins, K. A., Hois, S., Armstrong, J., & Donegan, S. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1680081 · Cited by 1
Act Local, Think Global: IR and Its Role in Immuno-Oncology in Hepatocellular Carcinoma
Usón, P. L. S., & Bekaii‐Saab, T. (2024) · Journal of Vascular and Interventional Radiology · doi:10.1016/j.jvir.2023.10.008 · Cited by 1
Integrating the new systemic treatment landscape and surgical therapy in hepatocellular carcinoma
Haber, P. K., Krenzien, F., Sarıbeyoğlu, K., Pratschke, J., & Schöning, W. (2024) · Turkish Journal of Surgery · doi:10.47717/turkjsurg.2024.6375 · Cited by 1
“Dual ICI combination durvalumab and tremelimumab has also increased survival relative to sorafenib and represents an alternative in frontline (33).”
BackgroundKuwano, A., Yada, M., Koga, Y., Tanaka, K., Ohishi, Y., Masumoto, A., & Motomura, K. (2024) · Oncology Letters · doi:10.3892/ol.2024.14442 · Cited by 1
“Recently, the combination of an ICI and a vascular endothelial growth factor inhibitor (atezolizumab plus beva‑ cizumab) and the combination of the ICIs tremelimumab and durvalumab were approved as systemic therapy options for patients with advanced HCC (4,8).”
BackgroundGan, Y., Shi, F., Zhu, H., Li, H., Han, S., & Li, D. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1256992 · Cited by 1
High Tumor Mutational Burden in Hepatocellular Carcinoma
Engle, J. A., Dibb, J., & Jakob, J. A. (2024) · Cureus · doi:10.7759/cureus.68132 · Cited by 1
“One of TMB’s most important clinical roles is the potential utility in predicting response to immunotherapies as they are developed [3].”
BackgroundInfluentialCsipak, A. R., da Fonseca, L. G., López, R. V. M., & Estevez-Diz, M. D. P. (2024) · Current Oncology · doi:10.3390/curroncol31110500 · Cited by 1
Transplant oncology: Concept, history, and evolution
Mazzaferro, V., Maspero, M., & Sposito, C. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21901-6.00001-x · Cited by 1
Ndirangu, K., Paine, A., Pilkington, H., & Trueman, D. (2024) · Advances in Therapy · doi:10.1007/s12325-024-03068-5 · Cited by 1
Chiang, C., Huang, K.-K., Lee, C., Hong, T., Wu, J.-S., Wu, H., Chang, T., Liu, Y., Chen, W.-T., Wang, C., et al. (2025) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359241312141 · Cited by 1
“31 Conversely, non-infiltrative HCC, characterized by distinct tumor borders and generally smaller sizes, may allow better local control through resection or ablation.”
Chan, K., Lai, Y., Hung, H., Lee, J., Cheng, C., Wang, Y.-C., Wu, T., Lee, C., Wu, T.-J., Chou, H., et al. (2025) · Cancers · doi:10.3390/cancers17020188 · Cited by 1
“Based on the current evidence, LT for HCC with PVTT remains controversial.”
Cirrhosis and complications hepatocellular carcinoma – expanding indications for immunotherapy
Degroote, H. (2024) · Acta Clinica Belgica · doi:10.1080/17843286.2025.2451429 · Cited by 1
“Durvalumab as monotherapy showed non-inferiority to sorafenib in the first line [9].”
Matono, T., Tada, T., Kumada, T., Hiraoka, A., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., et al. (2025) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16884 · Cited by 1
“More recently, in 2023, durvalumab and tremelimumab combination was developed as a first-line systemic therapy for HCC, based on the HIMALAYA trial [8].”
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
