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
Vogel, A., Meyer, T., Sapisochin, G., Salem, R., & Saborowski, A. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01200-4 · Cited by 2,427
Immune checkpoint therapy—current perspectives and future directions
Sharma, P., Goswami, S., Raychaudhuri, D., Siddiqui, B. A., Singh, P., Nagarajan, A., Liu, J., Subudhi, S. K., Poon, C., Gant, K. L., et al. (2023) · Cell · doi:10.1016/j.cell.2023.03.006 · Cited by 1,206
EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma
Sangro, B., Argemi, J., Ronot, M., Paradis, V., Meyer, T., Mazzaferro, V., Jepsen, P., Golfieri, R., Galle, P., Dawson, L., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2024.08.028 · Cited by 985
Self-citationSingal, A. G., Kanwal, F., & Llovet, J. M. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00825-3 · Cited by 1,029
“atezolizumab plus bevacizumab and durvalumab plus tremelimumab compared with camrelizumab plus rivoceranib (grade 3–4 in 43% and 26% versus 81% of patients, respectively) 177,178,186,234 .”
BackgroundInfluentialManagement of Hepatocellular Carcinoma
Brown, Z. J., Tsilimigras, D. I., Ruff, S. M., Mohseni, A., Kamel, I. R., Cloyd, J. M., & Pawlik, T. M. (2023) · JAMA Surgery · doi:10.1001/jamasurg.2022.7989 · Cited by 799
Qin, S., Chan, S. L., Gu, S., Bai, Y., Ren, Z., Lin, X., Chen, Z., Jia, W., Jin, Y., Guo, Y., et al. (2023) · The Lancet · doi:10.1016/s0140-6736(23)00961-3 · Cited by 746
Self-citationEvolving therapeutic landscape of advanced hepatocellular carcinoma
Yang, C. G., Zhang, H., Zhang, L., Zhu, A. X., Bernards, R., Qin, W., & Wang, C. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00704-9 · Cited by 747
Llovet, J. M., Kudo, M., Merle, P., Meyer, T., Qin, S., Ikeda, M., Xu, R., Edeline, J., Ryoo, B.-Y., Ren, Z., et al. (2023) · The Lancet Oncology · doi:10.1016/s1470-2045(23)00469-2 · Cited by 469
Self-citationSiegel, R. L., Kratzer, T. B., Wagle, N. S., Sung, H., & Jemal, A. (2026) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.70043 · Cited by 452
Precision treatment in advanced hepatocellular carcinoma
Yang, X., Yang, C. G., Zhang, S., Geng, H., Zhu, A. X., Bernards, R., Qin, W., Fan, J., Wang, C., & Gao, Q. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.01.007 · Cited by 466
Mechanisms of drug resistance in HCC
Ladd, A. D., Duarte, S. M., Şahin, İ., & Zarrinpar, A. (2023) · Hepatology · doi:10.1097/hep.0000000000000237 · Cited by 379
Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment
Llovet, J. M., Willoughby, C. E., Singal, A. G., Greten, T. F., Heikenwälder, M., El-Serag, H. B., Finn, R. S., & Friedman, S. L. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00754-7 · Cited by 354
Yau, T., Galle, P. R., Decaens, T., Sangro, B., Qin, S., da Fonseca, L. G., Karachiwala, H., Blanc, J.-F., Park, J.-W., Gane, E., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)00403-9 · Cited by 390
Self-citationCombination immunotherapy for hepatocellular carcinoma
Rimassa, L., Finn, R. S., & Sangro, B. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.03.003 · Cited by 377
Self-citationSangro, B., Chan, S. L., Kelley, R. K., Lau, G., Kudo, M., Sukeepaisarnjaroen, W., Yarchoan, M., De Toni, E. N., Furuse, J., Kang, Y. K., et al. (2024) · Annals of Oncology · doi:10.1016/j.annonc.2024.02.005 · Cited by 365
Self-citationSystemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update
Gordan, J. D., Kennedy, E. B., Abou‐Alfa, G. K., Beal, E. W., Finn, R. S., Gade, T. P. F., Goff, L. W., Gupta, S., Guy, J. E., Hoang, H. T., et al. (2024) · Journal of Clinical Oncology · doi:10.1200/jco.23.02745 · Cited by 349
Self-citationHepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment
Hwang, S. Y., Danpanichkul, P., Agopian, V. G., Mehta, N., Parikh, N. D., Abou‐Alfa, G. K., Singal, A. G., & Yang, J. D. (2024) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0824 · Cited by 359
Self-citationSangro, B., Kudo, M., Erinjeri, J. P., Qin, S., Ren, Z., Chan, S. L., Arai, Y., Heo, J., Mai, A., Escobar, J., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(24)02551-0 · Cited by 333
Self-citationQin, S., Kudo, M., Meyer, T., Bai, Y., Guo, Y., Meng, Z., Satoh, T., Marino, D., Assenat, E., Li, S., et al. (2023) · JAMA Oncology · doi:10.1001/jamaoncol.2023.4003 · Cited by 265
Self-citationYarchoan, M. M., Gane, E. J., Marron, T. U., Perales-Linares, R. F., Yan, J., Cooch, N. S., Shu, D. H., Fertig, E. J., Kagohara, L. T., Bartha, G. T., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02894-y · Cited by 284
“4–10,27).”
ResultBiomarkers for immunotherapy of hepatocellular carcinoma
Greten, T. F., Villanueva, A., Korangy, F., Ruf, B., Yarchoan, M., Ma, L., Ruppin, E., & Wang, X. W. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00816-4 · Cited by 227
“Similarly, at least one adverse event of grade 3–4 was detected in 50.5% of the patients receiving tremelimumab plus dur-valumab in the HIMALAYA study, of whom 12.6% had events deemed immune-related by the investigators 8 .”
BackgroundInfluentialBCLC strategy for prognosis prediction and treatment recommendations: The 2026 update
Reig, M., Sanduzzi‐Zamparelli, M., Forner, A., Rimola, J., Ferrer, J., Burrel, M., García‐Criado, Á., Díaz, A., Llarch, N., Iserte, G., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.10.020 · Cited by 253
Self-citationChan, S. L., Sun, H., Xu, Y., Zeng, H., El‐Serag, H. B., Lee, J. M., Schwartz, M., Finn, R. S., Seong, J., Wang, X. W., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01042-6 · Cited by 262
Self-citationQin, S., Chen, Z., Fang, W. J., Ren, Z., Xu, R., Ryoo, B., Meng, Z., Bai, Y., Chen, X., Liu, X., et al. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.22.00620 · Cited by 203
Self-citationA comprehensive review of immune checkpoint inhibitors for cancer treatment
Hossain, M. A. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113365 · Cited by 213
Rimassa, L., Chan, S. L., Sangro, B., Lau, G. K. K., Kudo, M., Reig, M., Breder, V. V., Ryu, M., Ostapenko, Y., Sukeepaisarnjaroen, W., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.03.033 · Cited by 190
Self-citationBreakthroughs in Hepatocellular Carcinoma Therapies
Singal, A. G., Kudo, M., & Bruix, J. (2023) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2023.01.039 · Cited by 167
Self-citationCappuyns, S., Corbett, V., Yarchoan, M., Finn, R. S., & Llovet, J. M. (2024) · JAMA Oncology · doi:10.1001/jamaoncol.2023.2677 · Cited by 167
Jin, Z., Chen, J.-J., Zhu, X., Duan, X.-H., Xin, Y., Zhong, B., Chen, J., Tie, J., Zhu, K., Zhang, L., et al. (2024) · EClinicalMedicine · doi:10.1016/j.eclinm.2024.102622 · Cited by 168
PD-1 and PD-L1 inhibitors in cold colorectal cancer: challenges and strategies
Lin, K. X., Istl, A. C., Quan, D., Skaro, A. I., Tang, E. S.-T., & Zheng, X. (2023) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-023-03520-5 · Cited by 172
Psyrri, A. K., Fayette, J., Harrington, K. J., Gillison, M. L., Ahn, M.-J., Takahashi, S., Weiss, J. M., Machiels, J.-P., Baxi, S. S., Vasilyev, A., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.12.008 · Cited by 153
Self-citationRecent advances in the management of hepatocellular carcinoma
Sankar, K. N., Gong, J., Osipov, A., Miles, S. A., Kosari, K., Nissen, N. N., Hendifar, A. E., Koltsova, E. K., & Yang, J. D. (2023) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2023.0125 · Cited by 156
Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma
Haber, P. K., Castet, F., Torres-Martin, M., Andreu-Oller, C., Puigvehí, M., Miho, M., Radu, P., Dufour, J.-F., Verslype, C., Zimpel, C., et al. (2023) · Gastroenterology · doi:10.1053/j.gastro.2022.09.005 · Cited by 145
Self-citationYahoo, N., Dudek, M., Knolle, P. A., & Heikenwälder, M. F. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.02.033 · Cited by 147
Immune checkpoint inhibitors in hepatocellular carcinoma: emerging challenges in clinical practice
Pinter, M., Scheiner, B., & Pinato, D. J. (2023) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(23)00147-4 · Cited by 139
Gardini, A. C., Rimini, M., Tada, T., Suda, G., Shimose, S., Kudo, M., Cheon, J., Finkelmeier, F., Lim, H. Y., Rimassa, L., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.11.017 · Cited by 137
Self-citationKinsey, E. N., & Lee, H. M. (2024) · Cancers · doi:10.3390/cancers16030666 · Cited by 145
“The HIMALAYA trial randomized 1171 patients with unresectable HCC requiring first-line systemic therapy to the combination of tremelimumab and durvalumab, durval-umab monotherapy, or sorafenib [87].”
BackgroundMASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges
Phoolchund, A. G. S., & Khakoo, S. I. (2024) · Cancers · doi:10.3390/cancers16020259 · Cited by 137
“The HIMALAYA study Phase III trial compared the PD-L1 inhibitor durval-umab in combination with the CTLA4 inhibitor tremelimumab (STRIIDE) versus sorafenib, with an improved OS (16.4 months vs. 13.7 months) [127].”
BackgroundInfluentialCurrent trends in sensitizing immune checkpoint inhibitors for cancer treatment
Wei, J., Li, W., Zhang, P., Guo, F., & Liu, M. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02179-5 · Cited by 144
Battle of the biopsies: Role of tissue and liquid biopsy in hepatocellular carcinoma
Lehrich, B. M., Zhang, J., Monga, S. P., & Dhanasekaran, R. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.11.030 · Cited by 126
TKIs in combination with immunotherapy for hepatocellular carcinoma
Stefanini, B., Ielasi, L., Chen, R., Abbati, C., Tonnini, M., Tovoli, F., & Granito, A. (2023) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2023.2181162 · Cited by 120
“Grade 3–4 side effects occurred in 51% of patients receiving STRIDE, 37% of patients receiving durvalumab, and 52% of patients receiving sorafenib [40].”
BackgroundImmune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy
Seyhan, D., Allaire, M., Fu, Y., Conti, F., Wang, X. W., Gao, B., & Lafdil, F. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01308-4 · Cited by 138
Chen, J., Feng, W., Sun, M., Huang, W., Wang, G., Chen, X., Yin, Y., Chen, X., Zhang, B., Nie, Y., et al. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.02.025 · Cited by 125
Rimini, M., Fornaro, L., Lonardi, S., Niger, M., Lavacchi, D., Pressiani, T., Lucchetti, J., Giordano, G., Pretta, A., Tamburini, E., et al. (2023) · Liver International · doi:10.1111/liv.15641 · Cited by 117
Self-citationKeam, S. J. (2022) · Drugs · doi:10.1007/s40265-022-01827-8 · Cited by 110
“Durvalumab monotherapy was noninferior to sorafenib in terms of OS in HIMALAYA [17].”
BackgroundMethodResultInfluentialThe extracellular matrix in hepatocellular carcinoma: Mechanisms and therapeutic vulnerability
Roy, A. M., Iyer, R. V., & Chakraborty, S. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101170 · Cited by 122
New concepts in the treatment of hepatocellular carcinoma
Sidali, S., Trépo, E., Sutter, O., & Nault, J. (2022) · United European Gastroenterology Journal · doi:10.1002/ueg2.12286 · Cited by 106
“0035).(59) Moreover, these CPI alone or in combination are tested currently as an”
BackgroundStereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma
Dawson, L. A., Winter, K. A., Knox, J. J., Zhu, A. X., Krishnan, S., Guha, C., Kachnic, L. A., Gillin, M. T., Hong, T. S., Craig, T., et al. (2024) · JAMA Oncology · doi:10.1001/jamaoncol.2024.5403 · Cited by 106
Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy
Luo, X., He, X., Zhang, X., Zhao, X., Zhang, Y., Shi, Y., & Hua, S. (2024) · MedComm · doi:10.1002/mco2.474 · Cited by 115
NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy
Pinter, M., Pinato, D. J., Ramadori, P., & Heikenwalder, M. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1258 · Cited by 103
“In addition, post hoc subgroup analysis from the HIMALAYA trial demonstrated improved OS for durvalumab plus tremelimumab versus sorafenib in patients with nonviral liver disease and HBV, but not in HCV-related HCC (55).”
MethodInfluentialRaimondi, A., Lonardi, S., Murgioni, S., Cardellino, G. G., Tamberi, S., Strippoli, A., Palermo, F., Manzoni, G. D., Bencivenga, M., Bittoni, A., et al. (2024) · Annals of Oncology · doi:10.1016/j.annonc.2024.11.016 · Cited by 105
Combination locoregional and systemic therapies in hepatocellular carcinoma
Zhong, B., Fan, W., Guan, J. J., Peng, Z., Jia, Z., Jin, H., Jin, Z.-C., Chen, J.-J., Zhu, H., & Teng, G. (2025) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(24)00247-4 · Cited by 111
Zhang, N., Yang, X., Piao, M., Xun, Z., Wang, Y., Ning, C., Zhang, L., Zhang, L., Wang, S., Wang, S., et al. (2024) · Biomarker Research · doi:10.1186/s40364-023-00535-z · Cited by 104
Melero, I., Yau, T., Kang, Y.-K., Kim, T.-Y., Santoro, A., Sangro, B., Kudo, M., Hou, M.-M., Matilla, A., Tovoli, F., et al. (2024) · Annals of Oncology · doi:10.1016/j.annonc.2024.03.005 · Cited by 101
Self-citationTabrizian, P., Holzner, M. L., Ajmera, V. H., Kim, A. K., Zhou, K., Schnickel, G. T., Torosian, K., Hoteit, M. A., Marino, R., Li, M., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.09.003 · Cited by 96
Yau, T., Kaseb, A., Cheng, A.-L., Qin, S., Zhu, A. X., Chan, S. L., Melkadze, T., Sukeepaisarnjaroen, W., Breder, V., Verset, G., et al. (2024) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(23)00454-5 · Cited by 97
Self-citationCappuyns, S., Philips, G., Vandecaveye, V., Boeckx, B., Schepers, R., Brussel, T. V., Arijs, I., Mechels, A., Bassez, A., Lodi, F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43381-1 · Cited by 97
Hepatocellular carcinoma: Epidemiology, diagnosis and treatment
Mauro, E., de Castro, T., Zeitlhoefler, M., Sung, M. W., Villanueva, A., Mazzaferro, V., & Llovet, J. M. (2025) · JHEP Reports · doi:10.1016/j.jhepr.2025.101571 · Cited by 104
Cho, Y., Kim, B. H., & Park, J. (2023) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2023.0099 · Cited by 87
Moris, D., Martinino, A., Schiltz, S., Allen, P. J., Barbas, A. S., Sudan, D. L., King, L. Y., Berg, C. L., Kim, C., Bashir, M. R., et al. (2025) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.70018 · Cited by 96
Fu, Q., Zheng, Y., Fang, W. J., Zhao, Q. D., Zhao, P., Liu, L., Zhai, Y., Tong, Z., Zhang, H., Lin, M., et al. (2023) · EClinicalMedicine · doi:10.1016/j.eclinm.2023.102175 · Cited by 88
Greten, T. F., Abou‐Alfa, G. K., Cheng, A., Duffy, A. G., El-Khoueiry, A. B., Finn, R. S., Galle, P. R., Goyal, L., He, A. R., Kaseb, A. O., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002794 · Cited by 81
Self-citationChen, E. X., Loree, J. M., Titmuss, E., Jonker, D. J., Kennecke, H. F., Berry, S. R., Couture, F., Ahmad, C. E., Goffin, J. R., Kavan, P., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.46094 · Cited by 85
Digestive cancers: mechanisms, therapeutics and management
Zhan, T., Betge, J., Schulte, N., Dreikhausen, L., Hirth, M., Li, M., Weidner, P., Leipertz, A., Teufel, A., & Ebert, M. P. A. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02097-4 · Cited by 90
Salié, H., Wischer, L., D’Alessio, A., Godbole, I., Suo, Y., Otto-Mora, P., Beck, J., Neumann, O., Stenzinger, A., Schirmacher, P., et al. (2024) · Gut · doi:10.1136/gutjnl-2024-332837 · Cited by 78
APASL clinical practice guidelines on systemic therapy for hepatocellular carcinoma-2024
Lau, G. K. K., Obi, S., Zhou, J., Tateishi, R., Qin, S., Zhao, H., Otsuka, M., Ogasawara, S., George, J., Chow, P. K. H., et al. (2024) · Hepatology International · doi:10.1007/s12072-024-10732-z · Cited by 90
“…global phase 3 clinical studies (REFLECT, IMbrave 150 and HIMALAYA) made lenvatinib, atezolizumab–bevacizumab and dual ICIs therapy with tremelimumab–dur-valumab as Single Tremelimumab Regular Interval Dur-valumab (STRIDE) therapy approved worldwide, as first-line therapy for uHCC [17, 19, 20, 24].”
Self-citationCelsa, C., Cabibbo, G., Fulgenzi, C. A. M., Scheiner, B., D’Alessio, A., Manfredi, G. F., Nishida, N., Ang, C., Marron, T. U., Saeed, A., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.10.040 · Cited by 76
Self-citationUpdates on Systemic Therapy for Hepatocellular Carcinoma
Ntellas, P., & Chau, I. (2024) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_430028 · Cited by 77
Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges
Zheng, S., Chan, S. W., Liu, F., Liu, J., Chow, P. K. H., Toh, H. C., & Hong, W. (2024) · Cancers · doi:10.3390/cancers16081582 · Cited by 80
“%) compared to Sorafenib [62,63].”
Self-citationRegorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial
Kim, H., Jung, S., Lim, H. Y., Ryoo, B., Ryu, M., Chuah, S., Chon, H. J., Kang, B., Hong, J. Y., Lee, H. C., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02824-y · Cited by 73
Finn, R. S., Ryoo, B., Hsu, C., Li, D., Burgoyne, A. M., Cotter, C., Badhrinarayanan, S., Wang, Y., Yin, A., Edubilli, T. R., et al. (2025) · The Lancet Oncology · doi:10.1016/s1470-2045(24)00679-x · Cited by 73
Immunotherapy for hepatocellular carcinoma: Recent advances and future targets
Yu, S. J. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108387 · Cited by 70
Patel, T. H., Brewer, J. R., Fan, J., Cheng, J., Shen, Y. L., Xiang, Y., Zhao, H., Lemery, S. J., Pazdur, R., Kluetz, P. G., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-2124 · Cited by 70
El-Khoueiry, A. B., Trojan, J., Meyer, T., Yau, T. C. C., Melero, I., Kudo, M., Hsu, C., Kim, T.-Y., Choo, S. P., Kang, Y., et al. (2023) · Annals of Oncology · doi:10.1016/j.annonc.2023.12.008 · Cited by 79
Self-citationArtificial intelligence in liver cancer — new tools for research and patient management
Caldéraro, J., Žigutytė, L., Truhn, D., Jaffe, A., & Kather, J. N. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00919-y · Cited by 73
“These treatments are not only more tolerable in terms of their general adverse effect profile but also substantially superior in terms of overall and progression-free survival 103,104 .”
Li, M., Bhoori, S., Mehta, N. J., & Mazzaferro, V. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.05.037 · Cited by 70
Guo, Z., Liu, Y., Ling, Q., Xu, L., Wang, T., Zhu, J., Lin, Y., Lu, X., Qu, W., Zhang, F., et al. (2024) · American Journal of Transplantation · doi:10.1016/j.ajt.2024.04.007 · Cited by 68
Yin, N., Li, X., Zhang, X., Xue, S., Cao, Y., Niedermann, G., Lu, Y., & Xue, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01826-z · Cited by 74
Celsa, C., Cabibbo, G., Fulgenzi, C. A. M., Battaglia, S. L., Enea, M., Scheiner, B., D’Alessio, A., Manfredi, G. F., Stefanini, B., Nishida, N., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000001026 · Cited by 73
Self-citationDhanasekaran, R., Hansen, A. S., Park, J., Lemaitre, L., Lai, I. K., Adeniji, N., Kuruvilla, S. P., Suresh, A., Zhang, J., Swamy, V., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0232 · Cited by 62
Yang, X., Chen, B., Wang, Y., Wang, Y., Long, J., Zhang, N., Xue, J., Xun, Z., Zhang, L., Cheng, J., et al. (2023) · Hepatology International · doi:10.1007/s12072-022-10480-y · Cited by 63
Zhou, J., Bai, L., Luo, J., Bai, Y., Pan, Y., Yang, X., Gao, Y., Shi, R.-S., Zhang, W., Zheng, J., et al. (2025) · The Lancet Oncology · doi:10.1016/s1470-2045(25)00190-1 · Cited by 69
Lee, Y. B., Nam, J. Y., Cho, E. J., Lee, J., Yu, S. J., Kim, H., Paeng, J. C., Yoon, J., & Kim, Y. J. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-0581 · Cited by 63
Chan, S. L., Ryoo, B., Mo, F. K. F., Chan, L. L., Cheon, J., Li, L., Wong, K. H., Yim, N., Kim, H., & Yoo, C. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.03.033 · Cited by 63
Self-citationScheiner, B., Roessler, D., Phen, S., Lim, M., Pomej, K., Pressiani, T., Cammarota, A., Fründt, T., von Felden, J., Schulze, K., et al. (2022) · JHEP Reports · doi:10.1016/j.jhepr.2022.100620 · Cited by 62
Self-citationTalamantes, S., Lisjak, M., Gilglioni, E. H., Llamoza-Torres, C. J., Ramos‐Molina, B., & Gurzov, E. N. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100811 · Cited by 62
Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations
Zhao, M. D., Guo, Z., Zou, Y., Li, X., Yan, Z.-P., Chen, M., Fan, W., Li, H.-L., Yang, J., Chen, X., et al. (2023) · Hepatology International · doi:10.1007/s12072-023-10599-6 · Cited by 65
“…or durvalumab) combined with either anti-angiogenesis (bevacizumab) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade (tremelimumab) are improved first-line systemic options for patients with unresectable HCC, which have shown to prolong OS compared with sorafenib [6, 7].”
InfluentialGarin, É., Tselikas, L., Guiu, B., Chalaye, J., Rolland, Y., de Baère, T., Assénat, E., Tacher, V., Palard, X., Deandreis, D., et al. (2024) · Journal of Nuclear Medicine · doi:10.2967/jnumed.123.266211 · Cited by 61
STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy
Gehrcken, L., Deben, C., Smits, E., & Audenaerde, J. R. M. V. (2025) · Advanced Science · doi:10.1002/advs.202500296 · Cited by 66
Zhou, J., Sun, H., Wang, Z., Cong, W., Zeng, M., Zhou, W., Liu, L., Wen, T., Kuang, M., Zhang, B., et al. (2025) · Liver Cancer · doi:10.1159/000546574 · Cited by 78
Treatment of portal hypertension in patients with HCC in the era of Baveno VII
Thabut, D., & Kudo, M. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.11.019 · Cited by 59
“In HIMALAYA trial, no bleeding event was observed in high dose tremelimumab/durvalumab (STRIDE regimen) arm[23].”
BackgroundSelf-citationCabibbo, G., Celsa, C., Rimassa, L., Torres, F., Rimola, J., Kloeckner, R., Bruix, J., Cammà, C., & Reig, M. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.01.018 · Cited by 62
Self-citationChen, K., Shuen, T. W. H., & Chow, P. K. H. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02684-w · Cited by 61
“Two years later, the combination of durvalumab (anti-PDL1) and tremelimu-mab (anti-CTLA4) was also approved by the FDA as a fi rst-line treatment of unresectable HCC (without main portal vein invasion) based on the HIMALAYA study [15].”
BackgroundInfluentialAbou‐Alfa, G. K., Galle, P. R., Chao, Y., Erinjeri, J. P., Heo, J., Borad, M. J., Luca, A., Burke, J., Pelusio, A., Agathon, D., et al. (2023) · Liver Cancer · doi:10.1159/000533650 · Cited by 57
Self-citationImmunotherapy for hepatocellular carcinoma
Childs, A., Aidoo-Micah, G., Maini, M. K., & Meyer, T. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2024.101130 · Cited by 64
Hepatocellular Carcinoma: Prevention, Diagnosis, and Treatment
Feng, F., & Zhao, Y. (2024) · Medical Principles and Practice · doi:10.1159/000539349 · Cited by 62
“For instance, in the recent HIMALAYA clinical study, tremelimumab in combination with durvalumab has been demonstrated to be superior to sorafenib in patients with unresectable HCC [96].”
Li, J., Liang, Y.-B., Wang, Q., Luo, W.-L., Chen, X., Lakang, Y., Yang, Z.-S., Zuo, J.-X., Li, Y.-K., Li, Z., et al. (2025) · Liver Cancer · doi:10.1159/000549355 · Cited by 67
Limousin, W., Laurent‐Puig, P., Ziol, M., Ganne‐Carrié, N., Nahon, P., Ait-Omar, A., Séror, O., Sidali, S., Campani, C., Blanc, P., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.08.017 · Cited by 55
Neoadjuvant and adjuvant systemic therapy in HCC: Current status and the future
Singal, A. G., Yarchoan, M. M., Yopp, A. C., Sapisochín, G., Pinato, D. J., & Pillai, A. A. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000430 · Cited by 55
Espinoza, M., Muquith, M., Lim, M., Zhu, H., Singal, A. G., & Hsiehchen, D. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.02.042 · Cited by 55
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
