Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2–3 study

Ren, Zhigang; Xu, Jianming; Bai, Yuxian; Xu, Anjian; Cang, Shundong; Du, Changsheng; Qiu, Li; 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; Shi, Xuetao; Gao, Zengqiang; Yin, Tao; Cui, Jiuwei; Huang, Ming; Xing, Baocai; Mao, Yilei; Teng, Gao‐Jun; Qin, Yanru; Wang, Jinhai; Xia, Feng; Yin, Guowen; Yang, Yong; Chen, Mingxia; Wang, Yan; Zhou, Hui; Fan, Jia

doi:10.1016/s1470-2045(21)00252-7

Cited by 656 publications

(594 citation statements)

References 27 publications

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“…9,12 In recent years, game-changing advances have been achieved in the development of therapies of various cancers, including melanoma, lung and liver cancers with immune checkpoint inhibitors (ICIs). [13][14][15] However, little success had been achieved in the use of ICIs in PDAC. 16 The relatively low rates of programmed cell death protein 1 (PD-1) expression, low mutational load and infiltration of T cells, and accumulation of regulatory T-cells (Tregs) could all lead to the failed immunotherapy in PDAC.…”

Section: Introductionmentioning

confidence: 99%

“…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. 35 Simultaneously, more and more studies indicated that IRE could further be an immune-stimulating method other than induce tumor cell death only.…”

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confidence: 99%

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Irreversible Electroporation Plus Anti-PD-1 Antibody versus Irreversible Electroporation Alone for Patients with Locally Advanced Pancreatic Cancer

He¹,

Sun²,

Li³

2021

JIR

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Background Irreversible electroporation (IRE) is shown to not only improve the prognosis of patients with locally advanced pancreatic cancer (LAPC) but also activate the immune system. Considering the immune-activating function of IRE, IRE may enhance the effect of immune checkpoint inhibitors in the treatment of LAPC. We aimed to compare the effect and safety of IRE combined with toripalimab versus IRE alone for LAPC. Methods We retrospectively collected data from LAPC patients treated with IRE plus toripalimab (240mg, 7 days after IRE) or IRE alone at Sun Yat‑sen University Cancer Center. Overall and progression-free survival and treatment-related adverse events were evaluated and compared. Results From August 2015 to June 2020, a total of 85 patients were collected and analyzed in this study: 70 in the IRE group and 15 in the IRE plus toripalimab group. The IRE plus toripalimab group showed longer OS [44.33 months (95% CI 17.39–71.27) versus 23.37 months (95% CI 21.20–25.54), P=0.010] and PFS [27.5 months (95% CI not reached) versus 10.6 months (95% CI 7.79–13.42), P=0.036], compared with IRE group. There were no treatment-related deaths in all patients of this study. Although pancreatic fistula, biliary fistula, abscess, vomiting and gastroparesis were a little more common in IRE plus toripalimab group, no significant differences in the rates of all adverse events between these two groups were observed. Conclusion IRE plus toripalimab had acceptable toxic effects and might improve survival in LAPC compared with IRE alone.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Irreversible Electroporation Plus Anti-PD-1 Antibody versus Irreversible Electroporation Alone for Patients with Locally Advanced Pancreatic Cancer

He¹,

Sun²,

Li³

2021

JIR

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“…Inspired by the landmark results of the IMbrave150 Phase III trial, immune-based combinations including durvalumab plus tremelimumab, cabozantinib plus atezolizumab, lenvatinib plus pembrolizumab, and nivolumab plus ipilimumab are under assessment, which may further modify the therapeutic scenario in patients with aHCC in the next 5 years (17,52). The recent ORIENT-32 study also reported an unprecedented benefit for sintilimab plus bevacizumab biosimilar versus sorafenib monotherapy in the first-line setting for Chinese patients with aHCC (53). We suggest that further efforts should be oriented towards the identification of potential populations who may benefit from immunotherapy and thus help in guiding individualized treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the clinicopathological features of HCC varies among different patient populations. For instance, patients with HBV-associated HCC in China are characterized by younger age, poor ECOG performance status, and increased risk of distant metastasis compared with patients in western countries (53). Thus, additional studies using the realworld data combined with clinical data from different endemic areas are warranted to evaluate the efficacy and safety of ICIbased immunotherapies.…”

Section: Discussionmentioning

confidence: 99%

Viral Status and Efficacy of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis

et al. 2021

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Background and AimImmune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to investigate the effects of viral etiology on response to ICIs in HCC and depict the tumor immune microenvironment (TIME) of virally infected and uninfected HCC.MethodsA systematic search was conducted in PubMed, Web of Science, Embase, and the Cochrane central register of controlled trials up to August 2021. Clinical trials reporting the efficacy of ICIs in HCC were eligible. Baseline characteristics including first author, year of publication, National Clinical Trials (NCT) registry number, study region, sample sizes, interventions, line of treatment, and viral status were extracted. Meta-analysis was conducted to generate combined odds ratios (ORs) with 95% confidence intervals (CI) based on random or fixed effect model, depending on heterogeneity. Tumor immune microenvironment was depicted using ESTIMATE and CIBERSORT algorithm.ResultsEight studies involving 1,520 patients were included. Combined data suggested that there was no significant difference of objective response rate (ORR) between virally infected HCC and non-viral HCC patients [OR = 1.03 (95% CI, 0.77–1.37; I2 = 30.9%, pH = 0.152)]. Similarly, difference was not observed on ORR between HBV-HCC and HCV-HCC patients [OR = 0.74 (95% CI, 0.52–1.06; I2 = 7.4%, pH = 0.374)]. The infiltration of immune cells in the tumor microenvironment did not differ by etiology except for M0 macrophages, M2 macrophages, regulatory T cells, naive B cells, follicular helper T cells, activated dendritic cells, activated mast cells, and plasma cells. Despite differences in infiltration observed in specific cell types, the immune score and stromal score were generally comparable among etiology groups.ConclusionViral etiology may not be considered as the selection criteria for patients receiving ICIs in HCC, and viral status has little impact on TIME remodeling during HCC tumorigenesis.

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“…Sintilimab, an anti-PD-1 antibody, in combination with a bevacizumab biosimilar, was studied in the first-line setting for advanced HCC in the phase II/III ORIENT-32 trial. 52 Patients were randomized to the combination therapy (n=380) or sorafenib (n=191) and stratified based on extrahepatic metastases, macrovascular invasion, AFP level, and performance status. With a median follow-up of 10 months, median OS was better in the experimental arm (not reached vs 10.4 months; HR=0.57; 95% CI 0.43-0.75; p<0.0001), as was PFS (4.6 vs 2.8 months; HR=0.56, 95% CI 0.46-0.70; p<0.0001), with an ORR of 20.3%.…”

Section: Sintilimab and Bevacizumabmentioning

confidence: 99%

Second-Line Treatment Options for Hepatocellular Carcinoma: Current Landscape and Future Direction

Pathak¹,

Sonbol²

2021

JHC

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Hepatocellular carcinoma is a leading cause of mortality worldwide, and its incidence is rising. The last few years have witnessed a proliferation of available systemic therapeutic options, with the approval of multiple agents, including immune checkpoint inhibitors and drugs targeting vascular endothelial growth factor, such as cabozantinib, regorafenib, and ramucirumab. Most recently, the combination of atezolizumab plus bevacizumab has resulted in the longest overall survival yet known in hepatocellular carcinoma, therefore changing the preferred first-line treatment from the previous options of sorafenib and lenvatinib. The aim of this review is to summarize the available clinical data for the current second-line systemic treatment options and the future perspectives in the treatment landscape of hepatocellular carcinoma.

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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

Cited by 656 publications

References 27 publications

Irreversible Electroporation Plus Anti-PD-1 Antibody versus Irreversible Electroporation Alone for Patients with Locally Advanced Pancreatic Cancer

Irreversible Electroporation Plus Anti-PD-1 Antibody versus Irreversible Electroporation Alone for Patients with Locally Advanced Pancreatic Cancer

Viral Status and Efficacy of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis

Second-Line Treatment Options for Hepatocellular Carcinoma: Current Landscape and Future Direction

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