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Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2–3 study
Abstract
Background China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma.Methods This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes.Findings Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause).Interpretation Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients.Funding Innovent Biologics.Translation For the Chinese translation of the abstract see Supplementary Materials section.
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“Combination therapies such as sintilimab plus anlotinib, sintilimab plus IBI305 (bevacizumab biosimilar), camrelizumab plus apatinib, and toripalimab plus axitinib demonstrated potent antitumor effects in multiple types of cancers [22, 114–120].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [119]
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
Cancer statistics in China, 2015
Chen, W., Zheng, R., Baade, P. D., Zhang, S., Zeng, H., Bray, F., Jemal, A., Yu, X. Q., & He, J. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21338 · Cited by 17,038
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
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089
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-citationCheng, A.-L., Kang, Y.-K., Chen, Z., Tsao, C.-J., Qin, S., Kim, J. S., Luo, R., Feng, J., Ye, S., Yang, T.-S., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70285-7 · Cited by 5,832
Self-citationSorafenib in Advanced Hepatocellular Carcinoma
정, 재. (2008) · Cited by 5,586
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
El-Khoueiry, A. B., Sangro, B., Yau, T., Crocenzi, T. S., Kudo, M., Hsu, C., Kim, T.-Y., Choo, S.-P., Trojan, J., Welling, T. H., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31046-2 · Cited by 4,280
Mok, T. S. K., Wu, Y.-L. L. C., Kudaba, I., Kowalski, D. M., Cho, B. C., Turna, H. Z., de Castro, G., Srimuninnimit, V., Лактионов, К. К., Bondarenko, I., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32409-7 · Cited by 3,357
Cited by
Sorted by citations
Items 101–200 of 1,000
Su, K., Liu, Y., Wang, P., He, K., Wang, F., Chi, H., Rao, M., Li, X., Wen, L., Song, Y., et al. (2022) · Hepatology International · doi:10.1007/s12072-022-10391-y · Cited by 51
Self-citationZhang, W., Zhang, K., Liu, C., Gao, W., Si, T., Zou, Q., Guo, Z., Yang, X., Li, M., Liu, D., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1127349 · Cited by 51
“In the ORIENT-32 trial, the effectiveness of combination therapy with sintilimab and a bevacizumab biosimilar (IBI305) was found to be superior to that of sorafenib monotherapy, which has been approved by the FDA for the first-line treatment of advanced unresectable liver disease (25).”
BackgroundSelf-citationYang, F., Xu, G., Huang, J., Yin, Y., Xiang, W., Zhong, B., Li, W.-C., Shen, J., Zhang, S., Yang, J., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.847601 · Cited by 50
“2 Sex Female 8 (15) 3 (15) Male 45 (85) 17 (85) Etiology Hepatitis B 47 (89) 19 (95) Others 6 (11) 1 (5) Child-Pugh class A 47 (89) 19 (95) B 6 (11) 1 (5) AFP <400 (IU/ml) 34 (64) 11 (55) ≥400 (IU/ml) 19 (36) 9 (45) Tumor distribution One hepatic lobe 36 (68) 16 (80) Two hepatic lobes 17 (32) 4 (20) Tumor burden <6 11…”
BackgroundLiu, K., Zhu, Y., & Zhu, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1103055 · Cited by 49
Wang, L., Li, L., & Zhou, W. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108634 · Cited by 51
Zhao, M., Pan, X., Yin, Y., Hu, H., Wei, J., Bai, Z., & Tang, W. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.869960 · Cited by 48
“Based on the published 14-month data of the phase II/III ORIENT-32 clinical trial (15) in Chinese patients with uHCC, the ORR of sintilimab (D) plus bevacizumab (hereinafter referred to as the “D + A” regimen) was 16% higher than that of the sorafenib regimen, and the OR and PFS rates were 0.”
BackgroundMethodVessels that encapsulate tumour clusters vascular pattern in hepatocellular carcinoma
Liu, K., Dennis, C. V., Prince, D. S., Marsh‐Wakefield, F., Santhakumar, C., Gamble, J. R., Strasser, S. I., & McCaughan, G. W. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100792 · Cited by 48
Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets
Pessino, G., Scotti, C., & Maggi, M. (2024) · Cancers · doi:10.3390/cancers16050901 · Cited by 50
“Sapanisertib, an mTOR inhibitor, is being tested in advanced or metastatic HCC patients (NCT02575339).”
Huang, J., Guo, Y., Huang, W., Hong, X., Quan, Y., Lin, L., Zhou, J., Liang, L., Zhang, Y., Zhou, J., et al. (2022) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s353956 · Cited by 48
Self-citationAdjuvant and neoadjuvant therapies for hepatocellular carcinoma
Vogel, A., Grant, R. C., Meyer, T., Sapisochín, G., O'Kane, G. M., & Saborowski, A. L. (2023) · Hepatology · doi:10.1097/hep.0000000000000726 · Cited by 53
Ding, Z., Dong, Z., Chen, Z., Hong, J., Yan, L., Li, H., Yao, S., Yan, Y., Yang, Y., Yang, C., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.733530 · Cited by 47
Self-citationSu, K., Guo, L., He, K., Rao, M., Zhang, J., Yang, X., Huang, W., Gu, T., Xu, K., Liu, Y., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.873830 · Cited by 46
“The combination therapy of PD-1/PD-L1 inhibitors with antiangiogenic drugs, such as pembrolizumab plus lenvatinib (5), sintilimab plus bevacizumab (6), and camrelizumab plus apatinib (7), attained good clinical results in advanced HCC patients and improved overall survival (OS) over single-agent therapy.”
BackgroundSelf-citationImmune checkpoint inhibitors and the liver: balancing therapeutic benefit and adverse events
Martin, E. D., Fulgenzi, C. A. M., Celsa, C., Laurent-Bellue, A., Torkpour, A., Lombardi, P., D’Alessio, A., & Pinato, D. J. (2024) · Gut · doi:10.1136/gutjnl-2024-332125 · Cited by 51
“21 While supported by a convincing rationale, ICI combinations with tyrosine kinase inhibitors (TKIs) failed to significantly improve OS in COSMIC-312, (atezolizumab plus cabozantinib vs sorafenib) 22 and LEAP-002 (pembrolizumab plus lenvatinib vs lenvatinib), 23 leaving camrelizumab plus…”
Su, K., Huang, W., Li, X., Xu, K., Gu, T., Liu, Y., Song, J., Qian, K., Xu, Y., Zeng, H., et al. (2023) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s398632 · Cited by 44
“A promising combined treatment approach that significantly increases the survival of HCC patients is ICI plus targeted drugs, such as lenvatinib + pembrolizumab, sintilimab + bevacizumab, and atezolizumab + bevacizumab.(4,5,31) Furthermore, our previous research discovered that programmed death 1 (PD-1) inhibitors com…”
BackgroundSelf-citationXiao, Y., Xu, Z., Cheng, Y., Huang, R., Xie, Y., Tsai, H., Zha, H., Xi, L., Wang, K., Cheng, X., et al. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00401-x · Cited by 44
Chen, Y., Zhang, J., Hu, W., Li, X., Sun, K., Shen, Y., Zhang, M., Wu, J., Gao, S., Yu, J., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01991-1 · Cited by 44
Self-citationMechanisms of drug resistance in hepatocellular carcinoma
Zou, Y., Wan, X., Zhou, Q., Zhu, G., Lin, S.-S., Tang, Q., Yang, X.-B., & Wang, S.-M. (2025) · Biological Procedures Online · doi:10.1186/s12575-025-00281-6 · Cited by 49
“Additionally, the combination of the anti-PD-1 antibody sintilimab and the biosimilar bevacizumab (IBI 305) has shown improved overall survival (OS) in Chinese patients with advanced HBV-related HCC compared to sorafenib [18].”
Fan, P., Qiang, H., Liu, Z., Zhao, Q., Wang, Y., Liu, T., Wang, X., Chu, T., Huang, Y., Xu, W., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.937924 · Cited by 41
Self-citationTao, S., Liang, S., Zeng, T., & Yin, D. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1043667 · Cited by 46
Huang, L., Zhu, H., & Shi, Y. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01734-x · Cited by 48
Chen, X., Li, W., Wu, X., Zhao, F., Wang, D., Wu, H., Gu, Y., Li, X., Qian, X., Hu, J., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.909035 · Cited by 43
“3% in the milestone IMbrave150 study (16, 30), suggesting that small molecule inhibitors of oncoangiogenesis might be more effective than antiangiogenic monoclonal antibodies in enhancing patient treatment response when in combination with an ICI.”
BackgroundSu, K., Wang, F., Li, X., Chi, H., Zhang, J., He, K., Wang, Z., Wen, L., Song, Y., Chen, J., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1265959 · Cited by 42
“001) were observed to be longer with sintilimab-bevacizumab compared with sorafenib (7).”
BackgroundRivera‐Esteban, J., Muñoz, S., Higuera, M., Sena, E., Bermúdez-Ramos, M., Bañares, J., Martínez-Gómez, M., Cusidó, M. S., Jiménez-Masip, A., Francque, S., et al. (2024) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2024.03.028 · Cited by 45
The current status and future of targeted-immune combination for hepatocellular carcinoma
Hao, L., Li, S., Ye, F., Wang, H., Zhong, Y., Zhang, X., Hu, X., & Huang, X. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1418965 · Cited by 49
Chen, H., Nio, K., Tang, H., Yamashita, T., Okada, H., Li, Y.-Y., Doan, P. T. B., Li, R., Lv, J., Sakai, Y., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031475 · Cited by 42
“In addition, a new TKI therapeutic strategy combining immune checkpoint inhibitors with inhibitors of vascular endothelial growth factor (VEGF), which enhances HCC angiogenesis, has been developed [3,4].”
BackgroundZheng, J., Shao, M., Yang, W., Ren, J., Chen, X., & Yang, H. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109244 · Cited by 41
Self-citationAdvances in pharmacokinetics and pharmacodynamics of PD-1/PD-L1 inhibitors
Yan, T., Yu, L., Shangguan, D., Li, W., Liu, N., Chen, Y., Fu, Y., Tang, J., & Liao, D. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109638 · Cited by 45
Self-citationKoustas, E., Trifylli, E.-M., Sarantis, P., Papadopoulos, N., Karapedi, E., Aloizos, G., Damaskos, C., Garmpis, N., Garmpi, A., Papavassiliou, K. A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126664 · Cited by 43
“This combinational treatment could be a potential novel therapeutic strategy, significantly improving the OS and progression-free survival (PFS), in comparison with sorafenib [110].”
ResultLi, X., Fu, Z., Chen, X., Cao, K., Zhong, J., Liu, L., Ding, N., Zhang, X., Zhai, J., & Qu, Z. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.950266 · Cited by 41
“The results showed a high ORR and DCR according to mRECIST of 69.3% and 80.7%, median PFS of 10.4 months, and median OS was 18.0 months.”
BackgroundInfluentialNing, C., Zhang, X., Wang, Y., Yang, X., Yang, X., Chao, J., Xun, Z., Xue, J., Wang, Y., Sun, H., et al. (2023) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2023.07.001 · Cited by 41
Self-citationWei, W., Ban, X., Yang, F., Li, J., Cheng, X., Zhang, R., Huang, X., Huang, Y., Li, Q., Qiu, Y., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-004338 · Cited by 40
Self-citationLiu, F., Li, X., Zhang, Y., Ge, S., Shi, Z., Liu, Q., & Jiang, S. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03490-9 · Cited by 45
Zhao, M., Huang, H., He, F., & Fu, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1188277 · Cited by 40
Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma
Akbulut, Z., Aru, B., Aydın, F., & Demirel, G. Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1379622 · Cited by 39
He, C., Sun, S., Zhang, Y., & Li, S. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s331023 · Cited by 37
“In recent years, along with the improvement in the ICIs, immune therapy became more and more popular in the treatment of several malignant tumors.(15,34) However, the immune-suppressive nature limited the efficacy of immune therapy in PDAC.”
BackgroundXu, D., Wang, H., Bao, Q., Jin, K., Liu, M., Liu, W., Yan, X., Wang, L., Zhang, Y., Wang, G., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56537-y · Cited by 40
“Several phase II/III trials showed promising ef fi cacy of ICIs in unresectable HCC 9,10 .”
Self-citationTong, J., Tan, Y., Ouyang, W., & Chang, H. (2025) · Experimental Hematology and Oncology · doi:10.1186/s40164-025-00636-5 · Cited by 43
Bejjani, A. C., & Finn, R. S. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.21.02605 · Cited by 36
Immunotherapy for hepatocellular carcinoma
Zhou, M., Liu, B., & Shen, J. (2022) · Clinical and Experimental Medicine · doi:10.1007/s10238-022-00874-5 · Cited by 36
“According to the available data, bevacizumab in combination with PD-1/PD-L1 monoclonal antibody was based on phase III studies with an ORR of 21% to 30%, and relatively mild adverse effects [7, 9].”
MethodSelf-citationLi, X., Chen, J., Liu, C., Song, X., Zhang, Y., Zhao, H., Yan, S., Jia, W., Wu, Z., Guo, Y., et al. (2024) · BMC Medicine · doi:10.1186/s12916-024-03356-5 · Cited by 36
“1 by IRC and 9.6 months by investigator review in current study, which was similar with that reported in large phase 3 trials, with PFS ranging from 5.6 to 8.2 months [9, 16, 17].”
MethodInfluentialSelf-citationYang, D.-L., Ye, L., Zeng, F.-J., Liu, J., Yao, H., Nong, J.-L., Liu, S., Peng, N., Li, W.-F., Wu, P., et al. (2025) · Hepatology · doi:10.1097/hep.0000000000001229 · Cited by 37
Self-citationTang, H., Cao, Y., Jian, Y., Li, X., Li, J., Zhang, W., Wan, T., Liu, Z., Tang, W., & Lu, S. (2022) · BioScience Trends · doi:10.5582/bst.2022.01019 · Cited by 35
Li, L., Wu, P., Liang, X., Chen, K., Zhang, G.-L., Su, Q.-B., Huo, R., Xie, R.-W., Huang, S. H., Ma, L., et al. (2023) · Journal of Gastroenterology · doi:10.1007/s00535-023-02018-2 · Cited by 36
“The findings of this study extend previous work establishing the efficacy of ICIs and TKIs as a first-line treatment of advanced HCC [17, 25, 26] to include a broader range of patients with intermediate or advanced disease, including patients at high risk of postoperative recurrence.”
ResultYe, P., Zeng, X., Peng, L., Liu, Q., Yi, L., Luo, X., Li, S., Wang, L., Qin, S., Wan, X., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.778505 · Cited by 36
“The burden of HCC in China is high, and the prognosis of patients with HCC is poor (Ren et al., 2021).”
BackgroundMethodResultInfluentialJi, J. H., Ha, S. Y., Lee, D., Sankar, K. N., Koltsova, E. K., Abou‐Alfa, G. K., & Yang, J. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087640 · Cited by 34
Peng, Z., Li, H., Gao, Y., Sun, L., Jiang, J., Xia, B., Huang, Y., Zhang, Y., Xia, Y., Zhang, Y., et al. (2024) · The Lancet Oncology · doi:10.1016/s1470-2045(24)00437-6 · Cited by 35
Self-citationCurrent Treatment Methods in Hepatocellular Carcinoma
Krupa, K., Fudalej, M. M., Cencelewicz-Lesikow, A., Badowska-Kozakiewicz, A. M., Czerw, A. I., & Deptała, A. (2024) · Cancers · doi:10.3390/cancers16234059 · Cited by 37
“The results showed that the combination has significantly greater OS and PFS than sorafenib, which could provide a novel treatment option for patients with unresectable, HBV-associated HCC [110].”
Zhang, J.-X., Chen, P., Liu, S., Zu, Q.-Q., Shi, H.-B., & Zhou, C.-G. (2022) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s358658 · Cited by 33
“It is possible that ICIs enhance the anti-tumor response of TACE, which could provide hope for patients with aggressive intermediate or advanced stage HCC.”
BackgroundInfluentialZhou, T., Cao, Y., Wang, X., Yang, L., Wang, Z., Ma, A., & Li, H. (2022) · Advances in Therapy · doi:10.1007/s12325-022-02079-4 · Cited by 34
“The subsequent treatment regimens and the proportion of patients using each scheme were derived from ORIENT-32 as well [9].”
BackgroundMethodResultInfluentialFu, Q., Chen, Y., Huang, D., Guo, C., Zhang, X., Xiao, W., Xue, X., Zhang, Q., Li, X., Gao, S., et al. (2023) · Annals of Surgical Oncology · doi:10.1245/s10434-023-13383-w · Cited by 35
Self-citationCrocetto, F., Ferro, M., Buonerba, C., Bardi, L., Dolce, P., Scafuri, L., Mirto, B. F., Verde, A., Sciarra, A., Barone, B., et al. (2023) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2023.104059 · Cited by 35
Chen, Y., Yang, P., Du, S., Zhuang, Y., Huang, C., Hu, Y., Zhu, W., Yu, Y., Liu, T., & Zeng, Z. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i24.3871 · Cited by 33
Self-citationZhu, H.-D., Liu, R., Jia, Z., Xia, D., Zhong, B., Fan, W., Lü, J., Zhao, M. D., & Teng, G. (2024) · EngMedicine · doi:10.1016/j.engmed.2024.100037 · Cited by 34
Self-citationLi, Q., Cao, M., Yuan, G., Cheng, X., Zang, M., Chen, M., Hu, X., Huang, J., Li, R., Guo, Y., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.809709 · Cited by 33
Self-citationHuang, J., Zhong, B., Jiang, N., Li, W.-C., Zhang, S., Yin, Y., Yang, J., Shen, J., Wang, W., & Zhu, X. (2022) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s386672 · Cited by 33
“Based on the efficacy results, the triple combination of TACE+IT was potentially an effective management option for advanced HCC.”
BackgroundResultInfluentialZhou, M., Zhu, S., Xu, C., Liu, B., & Shen, J. (2023) · Investigational New Drugs · doi:10.1007/s10637-023-01335-w · Cited by 33
Self-citationSun, J., Mao, F., Liu, C. X., Zhang, F., Jiang, D., Guo, W., Huo, L., Zhou, L., Lau, W. Y., Shi, J., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01604-3 · Cited by 32
“In addition to the IMbrave150 study and HIMALAYA trial, the ORIENT-32 study (sintilimab plus a bevacizumab biosimilar as first-line therapy) and the Keynote-394 study (pembrolizumab as second-line therapy) both disclosed encouraging results in 2021 and 2022.(28) However, these studies did not disclose the results when…”
ResultSelf-citationFu, Y., Guo, X., Sun, L., Cui, T., Wu, C., Wang, J., Liu, Y., & Liu, L. (2024) · eLife · doi:10.7554/elife.95009 · Cited by 31
“…study demonstrated superior OS and PFS with sindilizumab plus bevacizumab over sorafenib alone, with respective medians not reached and 10.4 months for OS (HR = 0.569, 95% CI 0.431–0.751, p 0.0001) and 4.5 vs 2.8 months for PFS (HR = 0.567, 95% CI 0.457–0.704, p 0.0001) ( Ren et al., 2021 ).”
BackgroundInfluentialSelf-citationShin, H., & Yu, S. J. (2025) · Journal of Liver Cancer · doi:10.17998/jlc.2025.02.03 · Cited by 32
“18,85,86 However, guidelines such as the BSG highlight that sintilimab plus IBI305 and camrelizumab plus rivoceranib have not been extensively evaluated in non-hepatitis B virus populations outside Asia, limiting their use as first-line therapies globally.”
Xie, Q., Zhang, P., Wang, Y., Mei, W., & Zeng, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.958720 · Cited by 35
Self-citationAchilles’ Heel of currently approved immune checkpoint inhibitors: immune related adverse events
Yan, T., Yu, L., Zhang, J., Chen, Y., Fu, Y., Tang, J., & Liao, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1292122 · Cited by 39
Self-citationPancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis
Zhang, T., Wang, Y., Shi, C., Liu, X., Lv, S., Wang, X., & Li, W. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.955701 · Cited by 31
“After screening and eligibility assessment, 50 clinical trials, including 35,223 patients with malignant tumors, were selected for inclusion in this meta-analysis (Figure 1) (Baas et al., 2021; Choueiri et al., 2021; Fennell et al., 2021; Gadgeel et al., 2020; Herbst et al., 2021; Janjigian et al., 2021; Monk et al.,…”
Self-citationShannon, A. H., Ruff, S. M., & Pawlik, T. M. (2022) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s383922 · Cited by 34
“The primary outcomes were median OS and PFS both of which were significantly longer in the sintilimab plus IBI305 group.(60) This data is encouraging for patients with hepatitis”
ResultAnti-PD-1/PD-L1 immunotherapy in conversion treatment of locally advanced hepatocellular carcinoma
Chen, J., Zhang, D., & Yuan, Y. (2022) · Clinical and Experimental Medicine · doi:10.1007/s10238-022-00873-6 · Cited by 30
Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma
Sadagopan, N., & He, A. R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021259 · Cited by 33
“This trial took place in 50 clinical sites in China, and 94% of the patients had HCC due to hepatitis B [29].”
BackgroundCai, M., Huang, W., Liang, W. Y., Guo, Y., Liang, L., Lin, L., Xie, L., Zhou, J., Chen, Y., Cao, B., et al. (2024) · Liver International · doi:10.1111/liv.15831 · Cited by 34
Self-citationTeng, W., Wang, H., Lin, S., & On behalf of Diagnosis Group and Systemic Therapy Group of TLCA (2024) · Liver Cancer · doi:10.1159/000537686 · Cited by 36
“Other combinations of antiangiogenic targeted therapy and PD-1/PD-L1 blockade, such as sintilimab plus IBI305 (bevacizumab biosimilar) (ORIENT-32) [105] showed a signi fi cant OS (HR, 0.57; p < 0.0001) and PFS (HR, 0.56; p < 0.0001) bene fi t versus sorafenib for Chinese patients with unresectable,…”
BackgroundInfluentialWang, S., Yuan, X., Yang, Z., Zhang, X., Xu, Z., Yang, L., Yang, X. Z., Zhou, W., & Liu, W. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.08.021 · Cited by 33
“Emerging evidence demonstrated that the treatment of sorafenib combined with immune checkpoint blockades (ICB) showed better anticancer activity in multiple tumors, including in HCC [25,26].”
Liu, W., Quan, B., Lu, S., Tang, B., Li, M., Chen, R., Ren, Z., & Yin, X. H. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.771045 · Cited by 30
Self-citationXiang, Y., Wang, K., Zheng, Y., Feng, S., Yu, H., Li, X.-W., Cheng, X., Cheng, Y., Feng, J.-K., Zhou, L.-P., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.839605 · Cited by 30
Self-citationZhou, T., Wang, X., Cao, Y., Yang, L., Wang, Z., Ma, A., & Li, H. (2022) · BMC Health Services Research · doi:10.1186/s12913-022-08661-4 · Cited by 30
“Patient cohort The baseline characteristics of the patients modelled in the PSM were assumed to be in line with the ORIENT-32 and REFLECT studies[6, 9].”
BackgroundMethodResultInfluentialWang, L., Wang, H., Cui, Y., Liu, M., Jin, K., Xu, D., Wang, K., & Xing, B. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1115109 · Cited by 30
“In this regard, the immune checkpoint inhibitor sintilimab, an anti-programmed cell death protein (PD-1) monoclonal antibody, has shown high anti-tumor activity in multiple tumor types (10).”
BackgroundSelf-citationBalcar, L., Scheiner, B., Fulgenzi, C. A. M., D’Alessio, A., Pomej, K., Roig, M. B., Meyer, E. L., Che, J., Nishida, N., Lee, P., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100982 · Cited by 30
Afra, F., Mahboobipour, A. A., Farid, A. S., & Ala, M. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115104 · Cited by 30
Galasso, L., Cerrito, L., Maccauro, V., Termite, F., Mignini, I., Esposto, G., Borriello, R., Ainora, M. E., Gasbarrini, A., & Zocco, M. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137191 · Cited by 28
“Another combination, sintilimab plus bevacizumab, is still being evaluated as a systemic first-line therapy primarily for HBV-associated HCC in a Chinese phase II/III trial [142].”
BackgroundMicrobiome meets immunotherapy: unlocking the hidden predictors of immune checkpoint inhibitors
Huang, L., Li, Y., Zhang, C., Jiang, A., Zhu, L., Mou, W., Li, K., Zhang, J., Cui, C., Cui, X., et al. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00819-2 · Cited by 28
Pelizzaro, F., Farinati, F., & Trevisani, F. (2023) · Biomedicines · doi:10.3390/biomedicines11041020 · Cited by 28
“ORIENT-32 [46] III Sintilimab + IBI305 (bevacizumab biosimilar) (n = 380) Sorafenib (n = 191) NE vs.”
BackgroundTranslational research on drug development and biomarker discovery for hepatocellular carcinoma
Chew, V., Chuang, C.-H., & Hsu, C. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01011-y · Cited by 29
Small-molecule-based targeted therapy in liver cancer
Ming, Y., Gong, Y., Fu, X., Ouyang, X., Peng, Y., & Pu, W. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.08.001 · Cited by 27
Lin, Z., Wang, W., Yan, Y., Ma, Z., Xiao, Z., & Mao, K. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000002322 · Cited by 27
Yao, J., Zhu, X., Wu, Z., Wei, Q., Cai, Y., Zheng, Y., Hu, X., Hu, H., Zhang, X., Pan, H., et al. (2022) · Cancer Medicine · doi:10.1002/cam4.4747 · Cited by 27
Wen, W., Zhang, Y., Zhang, H., & Chen, Y. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04057-3 · Cited by 28
“Ren/2021 (Ren et al., 2021) China 88 53 (21–82) 380 phase 2/3 NCT03794440 Sintilimab 200 mg, q3w Bevacizumab biosimilar”
BackgroundSelf-citationSun, K., Cao, S., Shi, F., Guan, Y., Tang, M. Y., Zhao, M., Jian, Y.-F., Cui, B., Li, Z., Wang, J., et al. (2022) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848221140662 · Cited by 27
Self-citationYue, B., Gao, Y., Hu, Y., Zhan, M., Wu, Y., & Lu, L. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1731 · Cited by 26
“…the anti-PD-1 antibody Sintilimab with Bevacizumab biosimilar (IBI305) improved overall survival (OS) in Chinese patients on late-stage HBV + HCC. 226 The pairing of the anti-PD-L1 antibody Atezolizumab with the anti-VEGF-A antibody Bevacizumab has set a new benchmark for first-line treatment,…”
BackgroundZhou, Y. J., Liu, Z., Yu, A., Zhao, G., & Chen, B. (2024) · ImmunoTargets and Therapy · doi:10.2147/itt.s494670 · Cited by 30
Tumor immunotherapy: Mechanisms and clinical applications
Nong, C., Guan, P., Li, L., Zhang, H., & Hu, H. (2022) · MedComm – Oncology · doi:10.1002/mog2.8 · Cited by 27
Strategies for improving the efficacy of immunotherapy in hepatocellular carcinoma
Zhu, Y., & Qin, L. (2022) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2022.08.003 · Cited by 26
Sun, H., Yang, H., & Mao, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1150151 · Cited by 28
“, 2020), sintilizumab and bevacizumab biosimilar IBI305, (Ren et al., 2021), camrelizumab Mab plus apatinib, (Xu et al.”
BackgroundSelf-citationEfficacy of immunotherapy in hepatocellular carcinoma: Does liver disease etiology have a role?
Pinto, E., Meneghel, P., Farinati, F., Russo, F. P., Pelizzaro, F., & Gambato, M. (2023) · Digestive and Liver Disease · doi:10.1016/j.dld.2023.08.062 · Cited by 27
New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma—Today and Tomorrow
Becht, R., Kiełbowski, K., & Wasilewicz, M. P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031456 · Cited by 29
“Patients in the study group achieved a significantly longer OS (HR = 0.57, p < 0.0001) as well as PFS (HR = 0.56, p < 0.0001) [133].”
BackgroundInfluentialSpatial single-cell omics: new insights into liver diseases
Suo, Y., Thimme, R., & Bengsch, B. (2025) · Gut · doi:10.1136/gutjnl-2024-332105 · Cited by 29
Cabibbo, G., Celsa, C., Bhoori, S., Reiberger, T., Pinato, D. J., & Cammà, C. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.07.020 · Cited by 30
Tan, D. J. H., Tang, A. S. P., Lim, W. H., Ng, C. H., Nah, B. K. Y., Fu, C. E., Xiao, J., Koh, B., Tay, P. W. L., Tan, E. X. X., et al. (2023) · Liver Cancer · doi:10.1159/000529824 · Cited by 25
Cao, F., Shi, C., Zhang, G., Luo, J., Zheng, J., & Hao, W. (2023) · BMC Cancer · doi:10.1186/s12885-023-11389-x · Cited by 25
“Both the IMbrave150 trial and ORIENT-32 trials demonstrated that immune checkpoint inhibitors (ICIs) combined with antiangiogenesis therapy significantly improved patient outcomes compared with sorafenib in advanced HCC patients who had not received systemic therapy [6, 7], and atezolizumab combined with bevacizumab (…”
BackgroundMa, S., He, Z., Liu, Y., Wang, L., Yang, S., Wu, Y., Chen, H., Wu, Y., & Wang, Q. (2024) · EClinicalMedicine · doi:10.1016/j.eclinm.2024.102543 · Cited by 25
Tang, C., He, Q., Feng, J., Liao, Z., Peng, Y., & Gao, J. X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1254158 · Cited by 24
Han, Z., Yang, F., Zhang, Y., Wang, J., Ni, Q., Zhu, H., Zhou, X. H., Gao, H., & Lu, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1029951 · Cited by 24
“8, P 0.0001), and the overall survival of the combination therapy was significantly better than that of sorafenib in the first overall survival analysis (ORIENT-32) (31).”
BackgroundInfluentialSelf-citationGuo, C., Zhang, J., Huang, X., Chen, Y., Sheng, J., Huang, X., Sun, J., Xiao, W., Sun, K., Gao, S., et al. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000054 · Cited by 24
Self-citationZhao, Z., Zhang, W., Pang, L., Zeng, L., Liu, S., & Liu, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1166299 · Cited by 25
“Zhenggang Ren (2021) (68) ORIENT-32 (NCT03794440) HCC Sintilimab + Bevacizumab 380 2”
BackgroundGong, Q., Chen, X., Liu, F., & Cao, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1216585 · Cited by 23
Metadata
- Authors
- Ren, Z., Xu, J., Bai, Y., Xu, A., Cang, S., Du, C., Li, Q., Lu, Y., Chen, Y., Guo, Y., Chen, Z., Liu, B., Jia, W., Wu, J., Wang, J., Shao, G., Zhang, B., Shan, Y., Meng, Z., Wu, J., Gu, S., Yang, W., Liu, C., Shi, X., Gao, Z., Yin, T., Cui, J., Huang, M., Xing, B., Mao, Y., Teng, G., Qin, Y., Wang, J., Xia, F., Yin, G., Yang, Y., Chen, M., Wang, Y., Zhou, H., & Fan, J.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Chinese PLA General Hospital (CN)
- Third Affiliated Hospital of Harbin Medical University (CN)
- Nantong University (CN)
- Henan Provincial People's Hospital (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Sichuan University (CN)
- Sun Yat-sen University (CN)
- Nanfang Hospital (CN)
- Second Affiliated Hospital of Anhui Medical University (CN)
- Nanjing Drum Tower Hospital (CN)
- Anhui Provincial Hospital (CN)
- Second Affiliated Hospital of Nanchang University (CN)
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Zhejiang Cancer Hospital (CN)
- Huazhong University of Science and Technology (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Fudan University (CN)
- Hunan Cancer Hospital (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Shandong Tumor Hospital (CN)
- First Affiliated Hospital of Bengbu Medical College (CN)
- Hubei Cancer Hospital (CN)
- First Hospital of Jilin University (CN)
- Peking Union Medical College Hospital (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Southwest Hospital (CN)
- Jiangsu Cancer Hospital (CN)
- Innovent Biologics (China) (CN)
- Corresponding author
- Fan, Jia
- ORCID
- Ren, Zhenggang
- Xu, Jianming
- Bai, Yuxian
- Xu, Aibing
- Cang, Shundong
- Du, Chengyou
- Li, Qiu
- Lu, Yinying
- Chen, Yajin
- Guo, Yabing
- Chen, Zhendong
- Liu, Baorui
- Jia, Weidong
- Wu, Jian
- Wang, Junye
- Shao, Guoliang
- Zhang, Bixiang
- Shan, Yunfeng
- Meng, Zhiqiang
- Wu, Jianbing
- Gu, Shanzhi
- Yang, Wei
- Liu, Chao
- Gao, Zhenyuan
- Yin, Tao
- Cui, Jiuwei
- Huang, Ming
- Mao, Yilei
- Qin, Yanru
- Wang, Jinhai
- Yin, Guowen
- Yang, Yong
- Chen, Mingxia
- Zhou, Hui
- Fan, Jia
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 22
- Issue
- 7
- Pages
- 977-990
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W3166753505
- Cited by
- 1,124
- References
- 30
- Citations by year
- 2026: 162 · 2025: 241 · 2024: 273 · 2023: 247 · 2022: 178 · 2021: 21
- FWCI
- 100.04
- Type
- journal article
- Language
- en
- Update notices
- erratum (2021-08-01)
- Open access
- closed
- Licence
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- sintilimab, bevacizumab biosimilar, sorafenib, hepatocellular carcinoma, PD-1 inhibitors, first-line therapy, unresectable liver cancer, hepatitis B virus, overall survival, progression-free survival, combination immunotherapy, anti-angiogenic therapy, China, safety and tolerability, macrovascular invasion
- MeSH terms
- Bevacizumab, Sorafenib, Progression-Free Survival, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, China, Female, Hepatitis B, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Time Factors, Disease Progression, Young Adult, Biosimilar Pharmaceuticals, Antibodies, Monoclonal, Humanized
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