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    Efficacy and Safety of SBRT Combined With Camrelizumab and Apatinib in HCC Patients With PVTT: Study Protocol of a Randomized Controlled Trial. Frontiers in oncology BACKGROUND:Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) has poor prognosis. Sorafenib/lenvatinib is recommended as the first-line therapy in these patients currently, with unsatisfactory response and survival benefit reported. Radiotherapy (RT) is increasingly utilized in advanced HCC and is considered an alternative option for HCC patients with PVTT. Combined treatment of RT and locoregional treatments such as transarterial chemoembolization shows promising results. However, the efficacy and safety for combined treatment of RT and systemic therapy have not been reported and thus warrant further studies. This prospective clinic trial aims at evaluating the efficacy and safety of stereotactic body RT (SBRT) combined with camrelizumab and apatinib in HCC patients with PVTT. METHODS:This multicenter, open-label, randomized controlled trial will enroll 264 HCC patients with PVTT who have not received systemic therapy previously. Stratification of patients will be based on the presence or absence of extrahepatic metastasis and level of AFP (AFP ≥ 400 or <400 ng/mL) and randomly assigned 1:1 to study and control groups. Patients in study group will receive SBRT (95% PTV 36-40 Gy/6-8 Gy), camrelizumab (200 mg every 3 weeks), and apatinib (250 mg every day), and patients in control group will receive camrelizumab (200 mg every 2 weeks) and apatinib (250 mg every day). Patients will be followed up for 1.5 to 3.5 years since the start of therapy. We will use overall survival as the primary endpoint and progression-free survival, objective response rate, disease control rate, adverse events, and quality of life as the secondary endpoints. DISCUSSION:This study will be the first randomized controlled trial to assess the efficacy and safety of SBRT combined with camrelizumab and apatinib for HCC patients with PVTT. The results may help establish a new standard first-line therapy for these patients. TRIAL REGISTRATION:Chinese Clinical Trial Registration No. ChiCTR1900027102. DATE OF REGISTRATION:October 31, 2019. 10.3389/fonc.2020.01589
    Early Prediction of Objective Response of Fibrinogen in a Real-World Cohort of Hepatocellular Carcinoma Cases Treated by Programmed Cell Death Receptor-1 and Lenvatinib. OncoTargets and therapy BACKGROUND:This cohort study aimed to investigate the influence of fibrinogen on progression-free survival and overall survival in unresectable HCC cases treated by PD-1 and lenvatinib. METHODS:A total of 57 unresectable HCC cases who received lenvatinib and PD-1, such as toripalimab, camrelizumab, or sintilimab, in Beijing Ditan Hospital Affiliated to Capital Medical University were enrolled in this study. RESULTS:Vascular invasion, high FIB (>2.83g/L), and metastasis were highly correlated with low PFS. There was a significant correlation between a raised risk of death and metastasis and increased FIB (>2.83g/L). CONCLUSION:FIB is associated with outcomes of unresectable HCC cases treated by PD-1 and lenvatinib. 10.2147/OTT.S332351
    Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial. Mei Kuimin,Qin Shukui,Chen Zhendong,Liu Ying,Wang Linna,Zou Jianjun Journal for immunotherapy of cancer BACKGROUND:Emerging clinical data suggest that an immune checkpoint inhibitor in combination with an antiangiogenic agent is a reasonable strategy for multiple malignancies. We assessed the combination of camrelizumab with apatinib in pretreated advanced primary liver cancer (PLC, cohort A) from a multicohort phase Ib/II trial. METHODS:Patients with PLC after prior systemic treatment(s) were administered camrelizumab (3 mg/kg, once every 2 weeks) plus apatinib (125, 250, 375, or 500 mg; once per day) in a 3+3 dose-escalation stage and subsequent expansion stage. The primary endpoints were tolerability and safety of study treatment. RESULTS:From April 2017 to July 2019, 28 patients (21 with hepatocellular carcinoma and 7 with intrahepatic cholangiocarcinoma) received camrelizumab plus apatinib. Two dose-limiting toxicities (both grade 3 diarrhea) were reported in the 500 mg cohort. Therefore, the 375 mg cohort was expanded. Of the 19 patients in the 375 mg cohort, dose reduction to 250 mg occurred in 8 patients within 2 months after treatment initiation. Of the 28 patients with PLC, 26 had grade ≥3 treatment-related adverse events, with hypertension being the most common (9/28). One treatment-related death occurred. The objective response rate was 10.7% (95% CI 2.3% to 28.2%). Median progression-free survival and overall survival were 3.7 months (95% CI 2.0 to 5.8) and 13.2 months (95% CI 8.9 to not reached), respectively. CONCLUSION:The combination of camrelizumab with apatinib had a manageable toxicity and promising antitumor activity in patients with advanced PLC. Apatinib at a dose of 250 mg is recommended as a combination therapy for further studies of advanced PLC treatment. TRIAL REGISTRATION NUMBERS:NCT03092895. 10.1136/jitc-2020-002191
    Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma. Wang Jiting,Li Jun,Tang Guiju,Tian Yuan,Su Song,Li Yaling Oncology letters Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5-30%. In China, HCC seriously threatens the nation's health; the incidence of HCC ranks fourth among all theriomas, and the mortality rate is the third highest worldwide. The main therapies for HCC are surgical treatment or liver transplantation; however, most patients with HCC will experience postoperative recurrence or metastasis, eventually resulting in mortality. As for advanced or unresectable HCC, the current appropriate treatment strategy is transarterial chemoembolization; however, limited therapeutic effect and natural or acquired drug resistance affect the efficacy of this approach. Previous studies have demonstrated that PD-L1 expression on host cells and myeloid cells plays an important role in PD-L1 blocked-mediated tumor regression. Thus, further research on programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is required. Countries including the United States, France, Britain and China have developed PD-1/PD-L1 blockers, including nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, toripalimab, sintilimab and camrelizumab. Notably, all of these blockers have therapeutic effect and influencing factors in HCC. Factors that influence the clinical outcome of PD-1 have also been discovered, such as inflammatory genes, specific receptors and signaling pathways. The discovery of these factors will help to identify novel methods, such as combination treatment, to decrease the influence of other factors on the efficacy of PD-1/PD-L1. Sorafenib and lenvatinib have been approved for first-line treatment for patients with advanced HCC. When first-line treatment frequently fails, pembrolizumab and ipilimumab plus nivolumab are used following sorafenib (but not lenvatinib) treatment in advanced HCC. Thus, tumor immunotherapy using PD-1/PD-L1 blockers exhibits promising outcomes for the treatment of HCC, and more novel PD-1/PD-L1 inhibitors are being developed to fight against this disease. The present review discusses the clinical results and influencing factors of PD-1/PD-L1 inhibitors in HCC to provide insight into the development and optimization of PD-1/PD-L1 inhibitors in the treatment of HCC. 10.3892/ol.2021.12540
    Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma. Zheng Yi,Wang Tingting,Tu Xiaoxuan,Huang Yun,Zhang Hangyu,Tan Di,Jiang Weiqin,Cai Shunfeng,Zhao Peng,Song Ruixue,Li Peilu,Qin Nan,Fang Weijia Journal for immunotherapy of cancer BACKGROUND:Checkpoint-blockade immunotherapy targeting programmed cell death protein 1 (PD-1) has recently shown promising efficacy in hepatocellular carcinoma (HCC). However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear. Herein, we report the dynamic variation characteristics and specificities of the gut microbiome during anti-PD-1 immunotherapy in HCC using metagenomic sequencing. RESULTS:Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders. For dynamic analysis during anti-PD-1 immunotherapy, the dissimilarity of beta diversity became prominent across patients as early as Week 6. In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12. Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified. The related functional genes and metabolic pathway analysis, such as carbohydrate metabolism and methanogenesis, verified the potential bioactivities of responder-enriched species. CONCLUSIONS:Gut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making. 10.1186/s40425-019-0650-9
    Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study. Xu Jianming,Zhang Yun,Jia Ru,Yue Chunyan,Chang Lianpeng,Liu Rongrui,Zhang Gairong,Zhao Chuanhua,Zhang Yaoyue,Chen Chunxia,Wang Yan,Yi Xin,Hu Zhiyuan,Zou Jianjun,Wang Quanren Clinical cancer research : an official journal of the American Association for Cancer Research PURPOSE:This study assessed the safety and efficacy of SHR-1210 (anti-PD-1 antibody) and apatinib (VEGFR2 inhibitor) as combination therapy in patients with advanced hepatocellular carcinoma (HCC), gastric, or esophagogastric junction cancer (GC/EGJC). PATIENTS AND METHODS:This was an open-label, dose-escalation (phase Ia) and expansion study (phase Ib). In phase Ia, patients ( = 15) received SHR-1210 200 mg every 2 weeks and apatinib 125-500 mg once daily until unacceptable toxicity or disease progression. In phase Ib, patients ( = 28) received apatinib at the phase Ia-identified recommended phase II dose (RP2D) plus SHR-1210. The primary objectives were safety and tolerability and RP2D determination. RESULTS:At data cutoff, 43 patients were enrolled. In phase Ia, four dose-limiting toxicity events were observed (26.7%): one grade 3 lipase elevation (6.7%) in the apatinib 250 mg cohort and three grade 3 pneumonitis events (20%) in the apatinib 500 mg cohort. The maximum tolerated RP2D for apatinib was 250 mg. Of the 33 patients treated with the R2PD combination, 20 (60.6%) experienced a grade ≥3 treatment-related adverse event; adverse events in ≥10% of patients were hypertension (15.2%) and increased aspartate aminotransferase (15.2%). The objective response rate in 39 evaluable patients was 30.8% (95% CI: 17.0%-47.6%). Eight of 16 evaluable HCC patients achieved a partial response (50.0%, 95% CI: 24.7%-75.4%). CONCLUSIONS:SHR-1210 and apatinib combination therapy demonstrated manageable toxicity in patients with HCC and GC/EGJC at recommended single-agent doses of both drugs. The RP2D for apatinib as combination therapy was 250 mg, which showed encouraging clinical activity in patients with advanced HCC. 10.1158/1078-0432.CCR-18-2484
    A Retrospective Study on Therapeutic Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors Plus Lenvatinib in Patients With Unresectable Hepatocellular Carcinoma. Technology in cancer research & treatment : We assessed the efficacy and safety of transarterial chemoembolization (TACE) in combination with lenvatinib plus programmed death receptor-1 (PD-1) signaling inhibitors (camrelizumab or sintilimab) in unresectable hepatocellular carcinoma (uHCC). : In this retrospective study, patients with uHCC were pretreated with lenvatinib for 1 to 2 weeks before TACE. Camrelizumab or sintilimab were initially administered intravenously in 1 week after TACE of a 21-day cycle. Primary objectives were objective response rate (ORR) and disease control rate (DCR) by modified Response Evaluation Criteria in Solid Tumors (mRECIST). The secondary endpoints included the progression-free survival (PFS), overall survival (OS), and toxicity. : Between March 5, 2019 and February 30, 2021, 53 patients were screened for eligibility. At data cutoff, 35.8% of patients remained on treatment. Median follow-up was 15.4 months. Confirmed ORR in the 51 evaluable patients was 54.9% (95% CI 41.4%-67.7%). DCR was 84.3% (95% CI 72.0%-91.8%). Median PFS was 8.5 months (95% CI 6.4 to 10.6 months). The median OS was not estimable. Grade ≥3 treatment-related adverse events occurred in 32.1% of patients. No new safety signals were identified. : TACE in combination with lenvatinib plus anti-PD-1 inhibitors may have promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals. 10.1177/15330338221075174
    Transarterial chemoembolization, ablation, tyrosine kinase inhibitors, and immunotherapy (TATI): A novel treatment for patients with advanced hepatocellular carcinoma. Meng Min,Li Wenhong,Yang Xia,Huang Guanghui,Wei Zhigang,Ni Yang,Han Xiaoying,Wang Jiao,Ye Xin Journal of cancer research and therapeutics Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Currently, the main effective treatment options for HCC include resection, liver transplantation, various percutaneous modalities (such as transarterial chemoembolization [TACE] and thermal ablation), and tyrosine kinase inhibitors (TKIs). Herein, we have proposed a novel therapy which consists of TACE, ablation, tyrosine kinase inhibitors, and immunotherapy (TATI) for patients with advanced HCC). We reported the therapeutic effects of TATI in four patients with advanced HCC. All patients underwent TACE treatment at the beginning of disease diagnosis. During follow-up, all patients were treated with microwave ablation because of a residual tumor or recurrence. For tumor control, apatinib, a TKI, was administered after ablation. If the tumor was resistant to the TKI, we continued to apatinib therapy in combination with immunotherapy (camrelizumab). All the four patients had better survival benefits and no serious adverse effects. 10.4103/jcrt.JCRT_101_20
    Camrelizumab Combined with FOLFOX4 Regimen as First-Line Therapy for Advanced Hepatocellular Carcinomas: A Sub-Cohort of a Multicenter Phase Ib/II Study. Li Hui,Qin Shukui,Liu Ying,Chen Zhendong,Ren Zhenggang,Xiong Jianping,Meng Zhiqiang,Zhang Xiao,Wang Linna,Zhang Xiaojing,Zou Jianjun Drug design, development and therapy Background:Immune checkpoint inhibitors and chemotherapy can synergistically increase efficacy in a variety of malignancies. We conducted this phase Ib/II study to assess the safety and efficacy of anti-PD-1 antibody camrelizumab in combination with FOLFOX4 for treatment-naive advanced hepatocellular carcinoma (aHCC). Methods:This open-label, multicenter phase Ib/II study (NCT03092895) enrolled patients with aHCC and without prior systemic treatment for treatment with camrelizumab (3 mg/kg) and FOLFOX4 every two weeks. First, six patients were enrolled, followed by an additional 28 patients after dose-limiting toxicity cases were determined to be <33% of patients. The primary endpoint was tolerability and safety of treatment. Results:A total of 34 aHCC patients were enrolled and received study treatment. No dose-limiting toxicity were observed in the first six patients enrolled. Twenty-nine (85.3%) of the total 34 patients had grade ≥3 treatment-related adverse events (TRAEs), with the most common ones being decreased neutrophil count (55.9%) and decreased white blood cell count (38.2%). No TRAEs-related deaths occurred. The objective response and disease control rate were 29.4% (95% CI, 15.1-47.5) and 79.4% (95% CI, 62.1-91.3), respectively. The median duration of response, progression-free survival, and overall survival was 6.9 months (range, 3.3-11.5), 7.4 months (95% CI, 3.9-9.2), and 11.7 months (95% CI, 8.2-22.0), respectively. Conclusion:Camrelizumab combined with FOLFOX4 for first-line treatment of patients with aHCC showed good safety and tolerability, with promising preliminary antitumor activity. 10.2147/DDDT.S304857
    Neoadjuvant Programmed Cell Death 1 (PD-1) Inhibitor Treatment in Patients With Hepatocellular Carcinoma Before Liver Transplant: A Cohort Study and Literature Review. Qiao Zi-Yun,Zhang Zi-Jie,Lv Zi-Cheng,Tong Huan,Xi Zhi-Feng,Wu Hao-Xiang,Chen Xiao-Song,Xia Lei,Feng Hao,Zhang Jian-Jun,Xia Qiang Frontiers in immunology Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring. 10.3389/fimmu.2021.653437
    Complete response of early stage hepatocellular carcinoma in a patient treated with combination therapy of camrelizumab (SHR-1210) and apatinib. Zhang Zeyu,Zhou Yufan,Hu Kuan,Li Zhecheng,Wang Zhiming,Huang Yun Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 10.1016/j.dld.2019.07.005
    Safety and Efficacy of Transarterial Chemoembolization and Immune Checkpoint Inhibition with Camrelizumab for Treatment of Unresectable Hepatocellular Carcinoma. Zhang Jin-Xing,Chen Pei,Liu Sheng,Zu Qing-Quan,Shi Hai-Bin,Zhou Chun-Gao Journal of hepatocellular carcinoma Background:The clinical outcomes of hepatocellular carcinoma (HCC) patients who receive transarterial chemoembolization (TACE) and immunotherapy are not well characterized. The present study evaluates the safety and efficacy of TACE in combination with immune checkpoint inhibitor treatment for unresectable HCC. Methods:A retrospective analysis of 34 HCC patients who received TACE and treatment with the immune checkpoint inhibitor (ICI), Camrelizumab, between July 2019 and May 2021, was performed. This included 21 patients who developed progressive disease and eight who remained stable after several sessions of TACE, along with five patients who were initially diagnosed with advanced HCC. Adverse events (AEs), objective response rate (ORR) according to modified response evaluation criteria in solid tumors, progression-free survival (PFS), and overall survival (OS) were evaluated. Results:The median follow-up from ICI initiation was 10.6 months (range: 2.4-25.0 months). Grade I/II and grade III/IV AEs from ICI treatment occurred in 20 (58.8%) and 2 patients (5.9%), respectively. Two to three months after ICI therapy, the ORR was 35.3% (12/34) and the median PFS and OS was 6.1 months (range: 1.1-19.3 months) and 13.3 months (range: 2.4-25.0 months), respectively. Conclusion:TACE in combination with ICI could be a promising treatment approach for unresectable HCC patients. 10.2147/JHC.S358658
    Interaction between hepatitis B virus infection and the efficacy of camrelizumab in combination with apatinib therapy in patients with hepatocellular carcinoma: a multicenter retrospective cohort study. Annals of translational medicine BACKGROUND:The interaction between hepatitis B virus (HBV) load and anti-programmed cell death (PD)-1 in combination with (+) antiangiogenic therapy remains controversial, especially for hepatocellular carcinoma (HCC) patients. This study sought to explore the effects of HBV load and antiviral therapy on anti-PD-1+ antiangiogenic therapy, and the rate of HBV reactivation during anti-PD-1+ antiangiogenic treatment. METHODS:We performed a multicenter retrospective cohort study of camrelizumab combined with apatinib (C+A) therapy between January 1, 2019 and January 1, 2021 in patients with unresectable HCC who were seropositive for hepatitis B surface antigen (HBsAg) and received antiviral therapy before C+A involvement. The effects of HBV load and antiviral therapy on C+A and the rate of HBV reactivation during C+A treatment were examined. RESULTS:Eighty-six patients were included in the analysis. The patients had a mean age of 55 years, and 72 (83.7%) were male. The objective response rates (ORRs) in patients with low (<2,000 IU/mL) and high (≥2,000 IU/mL) baseline HBV deoxyribonucleic acid (DNA) levels were 34.5% and 32.2%, respectively (χ=0.046; P=0.829), while the disease control rates (DCRs) were 67.3% and 80.6%, respectively (χ=1.762; P=0.184). The results of the univariate and multivariate analyses showed that the baseline HBV DNA level did not affect PD. Additionally, none of the 86 patients suffered from HBV reactivation or HBV-related hepatic impairment with continuous antiviral treatment, regardless of nucleos(t)ide analogue (NA) type (F=1.473; P=0.228). CONCLUSIONS:Baseline HBV loads did not affect the tumor responses of HCC patients receiving anti-PD-1+ antiangiogenic therapy. Thus, HBV reactivation should not be a contradiction for anti-PD-1+ antiangiogenic therapy among patients undergoing continuous and effective antiviral treatment. 10.21037/atm-21-3020
    Safety and Efficacy of Camrelizumab Combined with Apatinib for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Multicenter Retrospective Study. Yuan Guosheng,Cheng Xiao,Li Qi,Zang Mengya,Huang Wei,Fan Wenzhe,Wu Tao,Ruan Jian,Dai Wencong,Yu Wenxuan,Chen Mian,Guo Yabing,Hu Xiaoyun,Chen Jinzhang OncoTargets and therapy Introduction:Previous trials demonstrated that anti-angiogenesis or anti-programmed death protein 1 (PD-1) monotherapy showed unsatisfied effect in advanced hepatocellular carcinoma (HCC). No study existed that focus on the effects of camrelizumab and apatinib ("C+A") combination therapy for HCC patients with the location and extent of portal vein tumor thrombus (PVTT) as the main variable being assessed. This study was to compare the efficacy and tolerability of "C+A" for HCC patients with PVTT. Methods:We retrospectively analyzed patients with advanced HCC and PVTT who underwent "C+A" therapy in a multicenter retrospective cohort from Jan 2019 to July 2020. Outcomes of patients who underwent "C+A" were analyzed by using the Kaplan-Meier method according to types of PVTT: PVTT in the main portal vein (type A), PVTT in the first-order portal vein branch (type B), and PVTT in second- or lower-order portal vein branches (type C). Results:Sixty-three patients were finally included and the mean duration of follow-up was 12.6 ± 4.5 months. The objective response rate (ORR) and disease control rate (DCR) for the whole cohort were 44.0% and 75.0%, respectively. The median overall survival (OS), progression-free survival (PFS) and time to progression (TTP) were 14.8 months, 11.8 months and not yet reached (NR), respectively. Patients with type B (OS, 15.9 months; PFS, 14.0 months; TTP, NR) or type C (OS, 16.0 months; PFS, 14.9 months; NR) PVTT appear to have better survival benefits compared with type A (OS, 5.8 months; PFS, 5.0 months; TTP, 7.0 months). Along with AFP, the absence of main PVTT was an independent predictive factor for survival at uni- and multivariate analysis. Conclusion:Camrelizumab and apatinib yielded a promising outcome in patients with advanced HCC who developed a tumor thrombus in the first lower-order portal vein branches and was generally safe and had manageable side effects. 10.2147/OTT.S286169
    Combination of Sorafenib, Camrelizumab, Transcatheter Arterial Chemoembolization, and Stereotactic Body Radiation Therapy as a Novel Downstaging Strategy in Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Case Series Study. Frontiers in oncology BACKGROUND AND AIM:Although the treatment effect and availability of therapeutic options for advanced hepatocellular carcinoma (HCC) are limited, the downstaging strategy may improve patient prognosis. This study aimed to investigate the potential of combination therapy as a downstaging strategy for treating advanced HCC with portal vein tumor thrombus (PVTT). METHODS:This retrospective case series included patients having advanced HCC with PVTT, who received the combination therapy of sorafenib, camrelizumab, transcatheter arterial chemoembolization (TACE), and stereotactic body radiation therapy (SBRT) from January 2019 to December 2019 in Xiangya Hospital, Central South University. The downstaging rate, treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated. RESULTS:Of the 13 patients, HCC downstaging was achieved in 4 (33.3%) patients who later received hepatectomy. The overall response rate was 41.7%, and the disease control rate was 50.0%. The median PFS time was 15.7 months, with a 1-year PFS rate of 58.3%, whereas the median OS was not reached after 1 year (1-year OS, 83.3%). No severe adverse events or grade 3-4 adverse effect was observed in 12 of the 13 enrolled patients; therapy had to be discontinued in only one patient due to adverse events, who was excluded from the study. The most common adverse effect was fever ( = 4, 33.3%), followed by skin reaction ( = 3, 25%). CONCLUSION:A combination therapy comprising sorafenib, camrelizumab, TACE, and SBRT is an effective downstaging strategy for advanced HCC with PVTT and is associated with few adverse events. 10.3389/fonc.2021.650394
    Effectiveness and safety of toripalimab, camrelizumab, and sintilimab in a real-world cohort of hepatitis B virus associated hepatocellular carcinoma patients. Chen Jinzhang,Hu Xiaoyun,Li Qi,Dai Wencong,Cheng Xiao,Huang Wei,Yu Wenxuan,Chen Mian,Guo Yabing,Yuan Guosheng Annals of translational medicine Background:The clinical significance of programmed cell death protein-1 (PD-1)-targeted immunotherapy in Chinese patients is understudied. We thus aimed to evaluate the safety and efficacy of PD-1 inhibitors with toripalimab, camrelizumab or sintilimab for Chinese hepatocellular carcinoma (HCC) patients in a real-life cohort. Methods:We analysed hepatitis B virus (HBV)-associated HCC patients treated with toripalimab, camrelizumab, or sintilimab in a retrospective single-center cohort from November 2018 to June 2020. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), time to tumor progression (TTP), and overall survival (OS). Safety data were also recorded. Results:Seventy patients were finally included in the analysis: 23 were treated with toripalimab, 33 with camrelizumab, and 14 with sintilimab. The mean duration of follow-up was 44.7 (95% CI: 39.9-49.6) weeks and the mean cycles of PD-1 at cutoff were 8.3±8.0 for all patients. The ORR and DCR for the whole cohort were 30% and 72.9%, respectively. Overall, 25 (35.7%) patients had radiological disease progression and 10 (14.3%) patients died during follow-up. Median PFS, median TTP, and median OS had not yet been reached. Most frequent drug-related adverse events (AEs) were rash (27.1%), hypertension (18.6%), fatigue (17.1%), diarrhea (17.1%), paresthesia (15.7%), and nausea (15.7%). Conclusions:Our findings suggest that (I) PD-1 targeted immunotherapy with toripalimab, camrelizumab, or sintilimab yielded a promising outcome in Chinese HBV patients with HCC and that (II) immunotherapy was well tolerated generally and had manageable side effects. This approach thus warrants further popularization and application in clinical practice. 10.21037/atm-20-6063
    Comprehensive Treatment of Trans-Arterial Chemoembolization Plus Lenvatinib Followed by Camrelizumab for Advanced Hepatocellular Carcinoma Patients. Liu Juanfang,Li Zhen,Zhang Wenguang,Lu Huibin,Sun Zhanguo,Wang Guozheng,Han Xinwei Frontiers in pharmacology This study aimed to report the efficacy and safety of -arterial chemoembolization (TACE) plus lenvatinib and camrelizumab in patients with advanced hepatocellular carcinoma (HCC). This retrospective study enrolled 22 patients with advanced HCC from March 2018 to December 2019. All the patients received comprehensive treatment with TACE plus lenvatinib followed by camrelizumab. Overall survival (OS) and progression-free survival (PFS) were calculated and analysed using the Kaplan-Meier method and log-rank test. Treatment response and adverse events (AEs) were also evaluated. The objective response rate (ORR) and disease control rate (DCR) for the whole cohort were 68.2 and 100% at the first month and 72.7 and 95.5% at the third month, respectively. The median OS was 24 months (95% CI, 20.323-27.677 months), and the median PFS was 11.4 months (95% CI, 8.846-13.954 months). The majority of treatment-related adverse reactions were mild or moderate, except for 4 that developed to grade 3-4 (3 reactions of grade 3, 1 reaction of grade 4). No deaths or other serious adverse reactions occurred. -arterial chemoembolization plus lenvatinib and camrelizumab shows good results incontrolling tumour progression and prolonging median OS in patients with advanced HCC. 10.3389/fphar.2021.709060
    Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study. Li Qi,Cao Mengran,Yuan Guosheng,Cheng Xiao,Zang Mengya,Chen Ming,Hu Xiaoyun,Huang Jing,Li Rong,Guo Yabing,Ruan Jian,Chen Jinzhang Frontiers in oncology Background:Combining an antiangiogenic agent with an anti-PD-1 agent is a promising strategy for unresectable hepatocellular carcinoma (HCC). Aims:To explore the effectiveness and tolerability of lenvatinib plus camrelizumab vs. lenvatinib monotherapy as a first-line treatment for unresectable HCC. Methods:This multicenter, retrospective cohort study included patients with unresectable HCC treated with oral lenvatinib 8 mg daily and intravenous camrelizumab 200 mg every 3 weeks (L+C group) or lenvatinib 12 mg or 8 mg daily (L group) in four Chinese centers between September 2018 and February 2020. Tumor response was evaluated according to RECIST 1.1 and mRECIST. The outcomes included objective response rate (ORR), overall survival (OS), 1-year OS rate, progression-free survival (PFS), and safety. Results:By March 31, 2021, 92 patients were finally included, with 48 and 44 in the L+C and L groups, respectively. ORR was significantly higher in the L+C group than in the L group (RECIST 1.1: 37.5% vs. 13.6%, P=0.009; mRECIST: 41.7% vs. 20.5%, P=0.029). Median OS and 95% confidence interval (CI) was 13.9 (13.3-18.3) months in the L group and not reached in the L+C group (P=0.015). The 1-year survival rate was 79.2% and 56.8% in the L+C and L groups, respectively. Median PFS was 10.3 (6.6-14.0) months and 7.5 (5.7-9.3) months in the L+C and L groups, respectively (P=0.0098). Combined therapy vs. monotherapy was independently associated with a prolonged OS (hazard ratio=0.380, 95% CI=: 0.196-0.739, P=0.004) and a prolonged PFS (hazard ratio=0.454, 95%CI=0.282-0.731, P=0.001). The safety profile was comparable between the two groups. The most common adverse event in the L+C and L groups was loss of appetite (41.7% vs. 40.9%, P=0.941). Three patients in the L+C group and two in the L group terminated treatment owing to adverse events. Conclusion:First-line lenvatinib plus camrelizumab showed better effectiveness than lenvatinib alone in patients with unresectable HCC. 10.3389/fonc.2022.809709
    Camrelizumab Plus Sorafenib Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Analysis. Frontiers in oncology BACKGROUND:Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis. Immunotherapy has gained great interest for various solid tumors due to its promising clinical efficacy. Targeted therapy also plays a crucial role in anticancer treatment. However, studies on the combination of immunotherapy and targeted therapy for advanced HCC are limited. Thus, the objective of this study was to investigate the efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced HCC. METHODS:From January 2019 to January 2021, 100 consecutive patients with advanced HCC in our hospital were enrolled for this study. Patients were assigned into two groups: a combined-therapy group (camrelizumab + sorafenib) and a sorafenib-only group. Progression-free survival (PFS), overall survival (OS), treatment response, and relevant adverse effects (AEs) were evaluated and recorded. RESULTS:Of a total of 100 patients, 35 received a combination of camrelizumab and sorafenib, and 65 were treated with sorafenib alone. After 1:1 propensity score matching (PSM), each group had 34 patients. The overall response rate (ORR) of the combined-therapy group was statistically significantly higher than that of the sorafenib-only group (before PSM, = 0.037; after PSM, = 0.010). However, there was no significant difference in disease control rate (DCR) between the two groups (before PSM, = 0.695; after PSM, = 1.000). Patients who received the combination therapy had significantly longer PFS than those who received the sorafenib monotherapy (before PSM, = 0.041; after PSM, = 0.043). However, the two groups exhibited comparable median OS (before PSM, = 0.135; after PSM, = 0.105). Although the combined-therapy group showed a higher incidence of AEs such as thrombocytopenia than the sorafenib-only group after PSM, most of these AEs were easily controlled after treatment. CONCLUSION:Camrelizumab plus sorafenib showed favorable efficacy and manageable toxicity for patients with advanced HCC. However, more prospective randomized trials are necessary to further verify the potential clinical benefits of this combination therapy. 10.3389/fonc.2021.694409
    Apatinib Plus Camrelizumab With/Without Chemoembolization for Hepatocellular Carcinoma: A Real-World Experience of a Single Center. Frontiers in oncology OBJECTIVE:This study was conducted in order to compare the efficacy and safety of transarterial chemoembolization (TACE) plus apatinib plus camrelizumab (TACE+AC) and apatinib plus camrelizumab (AC) in the treatment of unresectable hepatocellular carcinoma (HCC) in a real-world setting. METHODS:In this single-center retrospective study, the data of patients with unresectable HCC who had received TACE+AC or AC treatment during March 2017 to May 2021 were assessed. Patients in the AC group received intravenous administration of camrelizumab 200 mg every 3 weeks and oral apatinib 250 mg/day treatment. Patients in the TACE+AC group received the same dose of camrelizumab and apatinib 1 week after TACE. The primary endpoint of the study was overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) as the secondary endpoints. RESULTS:A total of 108 patients were enrolled in the study. There were 52 patients in the AC group and 56 patients in TACE+AC group. Median OS was significantly longer in the TACE+AC group than in the AC group (24.8 vs. 13.1 months; = 0.005). Patients in the TACE+AC group achieved a higher ORR [24 (42.9%) vs. 9 (17.3%), = 0.004] than those in the AC group. Patients in the TACE+AC group also achieved a higher disease control rate (DCR) [48 (85.7%) vs. 30 (57.7%), = 0.001] than patients in the AC group. There was no significant difference in the incidence of AEs related to apatinib and camrelizumab between the two groups, except for gastrointestinal reaction ( > 0.05, all; < 0.05, gastrointestinal reaction). CONCLUSION:TACE plus apatinib plus camrelizumab significantly improved OS, ORR, and DCR over apatinib plus camrelizumab in patients with unresectable HCC. AEs were tolerable and manageable. 10.3389/fonc.2021.835889
    A Phase 2 Study of Camrelizumab for Advanced Hepatocellular Carcinoma: Two-Year Outcomes and Continued Treatment beyond First RECIST-Defined Progression. Liver cancer INTRODUCTION:In a multicenter, open-label, parallel-group, randomized, phase 2 study for pretreated advanced hepatocellular carcinoma (HCC), camrelizumab showed potent antitumor activity and acceptable safety profile. The aim of this report was to provide long-term data and evaluate potential benefit of treatment with camrelizumab beyond progression. METHODS:From November 15, 2016, to November 16, 2017, 217 patients received camrelizumab 3 mg/kg intravenously every 2 or 3 weeks. Treatment beyond first Response Evaluation Criteria in Solid Tumors (RECIST)-defined progression (TBP) with camrelizumab was allowed. RESULTS:At data cutoff of December 16, 2019 (>2 years after the last patient enrollment; median duration of follow-up, 13.2 months [IQR 5.7-25.8]), 14 (43.8%) of the 32 responses per blinded independent central review were ongoing. The median duration of response was not reached (range 2.5-30.5 + months). The ongoing response rates at 12, 18, and 24 months were 68.3% (95% confidence interval [CI] 47.7-82.2), 59.8% (95% CI 38.8-75.6), and 53.1% (95% CI 31.0-71.0), respectively. The median overall survival (OS) was 14.2 months (95% CI 11.5-16.3). The 18- and 24-month OS rates were 41.3% (95% CI 34.6-47.9) and 33.7% (95% CI 27.3-40.2), respectively. Of the 172 patients who experienced RECIST-defined progression per investigator, 102 received TBP, while 70 did not (non-TBP). The median OS was 16.9 months (95% CI 13.3-22.6) in the TBP group versus 9.4 months (95% CI 5.8-14.8) in the non-TBP group, and the 18- and 24-month OS rates were 47.5% (95% CI 37.3-56.9) versus 33.1% (95% CI 22.3-44.3) and 38.8% (95% CI 29.2-48.4) versus 23.2% (95% CI 13.8-34.1), respectively. No new safety signals of camrelizumab were observed. CONCLUSIONS:With prolonged follow-up, camrelizumab continues to demonstrate the durable response and long survival in pretreated advanced HCC patients with manageable toxicities, especially in those who continued the treatment beyond first RECIST-defined progression. 10.1159/000516470
    Lenvatinib Plus Camrelizumab versus Lenvatinib Monotherapy as Post-Progression Treatment for Advanced Hepatocellular Carcinoma: A Short-Term Prognostic Study. Cancer management and research OBJECTIVE:Compared the outcomes between lenvatinib plus camrelizumab therapy and lenvatinib monotherapy as post-progression treatment for advanced hepatocellular carcinoma (HCC) with progressive disease (PD). PATIENTS AND METHODS:A total of 48 advanced HCC patients were included in this retrospective study between June 2019 and March 2020. The patients were divided into the lenvatinib plus camrelizumab group (n=21) and the lenvatinib group (n=27). Primary endpoints were overall survival (OS) and progression-free survival (PFS), and secondary endpoints were the objective response rate (ORR) and adverse events (AEs). RESULTS:The median follow-up time was 8.4 months. The median OS was not obtained. The median PFS of lenvatinib plus camrelizumab group was significantly longer than that of lenvatinib group (8.0 months vs 4.0 months, =0.011). Compared with lenvatinib group, lenvatinib plus camrelizumab group had higher ORR (28.57% vs 7.41%) and disease control rate (DCR) (71.43% vs 51.85%). The most common adverse events (AEs) included hand-foot skin reaction, hypertensions and abnormal hepatic function damage. Overall, 23.81% and 25.93% of patients experienced grade ≥3AEs in the lenvatinib plus camrelizumab group and the lenvatinib group, respectively. CONCLUSION:Lenvatinib plus camrelizumab as post-progression treatment is effective and safe for advanced hepatocellular carcinoma with PD. 10.2147/CMAR.S304820
    Efficacy and Safety of the Combination of Transarterial Chemoembolization with Camrelizumab plus Apatinib for Advanced Hepatocellular Carcinoma: A Retrospective Study of 38 Patients from a Single Center. Canadian journal of gastroenterology & hepatology Objective:To evaluate the effectiveness and safety of transarterial chemoembolization (TACE) combined with immune checkpoint inhibition (camrelizumab) plus an antiangiogenic agent (apatinib) for advanced hepatocellular carcinoma (HCC). Methods:Between March 2019 and April 2021, the clinical data of 38 patients diagnosed with advanced HCC who initially received TACE combined with camrelizumab plus apatinib were reviewed retrospectively. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results:At 2-3 months after initial therapy, the ORR and DCR was 50.0% (19/38) and 76.3% (29/38), respectively. The median PFS and OS were 7.3 months (range: 1.0-22.6 months) and 13.5 months (range: 2.3-24.3 months), respectively. Treatment-related AEs (grades 3-4) were observed in 25 patients (67.8%). No treatment-related deaths occurred. Conclusion:The combination of TACE with camrelizumab plus apatinib for the treatment of patients with advanced HCC showed promising efficacy and a manageable safety profile. 10.1155/2022/7982118
    Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Qin Shukui,Ren Zhenggang,Meng Zhiqiang,Chen Zhendong,Chai Xiaoli,Xiong Jianping,Bai Yuxian,Yang Lin,Zhu Hong,Fang Weijia,Lin Xiaoyan,Chen Xiaoming,Li Enxiao,Wang Linna,Chen Chunxia,Zou Jianjun The Lancet. Oncology BACKGROUND:Blocking the interaction between PD-1 and its ligands is a promising treatment strategy for advanced hepatocellular carcinoma. This study aimed to assess the antitumour activity and safety of the anti-PD-1 inhibitor camrelizumab in pretreated patients with advanced hepatocellular carcinoma. METHODS:This is a multicentre, open-label, parallel-group, randomised, phase 2 trial done at 13 study sites in China. Eligible patients were aged 18 years and older with a histological or cytological diagnosis of advanced hepatocellular carcinoma, had progressed on or were intolerant to previous systemic treatment, and had an Eastern Cooperative Oncology Group performance score of 0-1. Patients were randomly assigned (1:1) to receive camrelizumab 3 mg/kg intravenously every 2 or 3 weeks, via a centralised interactive web-response system using block randomisation (block size of four). The primary endpoints were objective response (per blinded independent central review) and 6-month overall survival, in all randomly assigned patients who had at least one dose of study treatment. Safety was analysed in all treated patients. This study is registered with ClinicalTrials.gov, number NCT02989922, and follow-up is ongoing, but enrolment is closed. FINDINGS:Between Nov 15, 2016, and Nov 16, 2017, 303 patients were screened for eligibility, of whom 220 eligible patients were randomly assigned and among whom 217 received camrelizumab (109 patients were given treatment every 2 weeks and 108 every 3 weeks). Median follow-up was 12·5 months (IQR 5·7-15·5). Objective response was reported in 32 (14·7%; 95% CI 10·3-20·2) of 217 patients. The overall survival probability at 6 months was 74·4% (95% CI 68·0-79·7)]. Grade 3 or 4 treatment-related adverse events occurred in 47 (22%) of 217 patients; the most common were increased aspartate aminotransferase (ten [5%]) and decreased neutrophil count (seven [3%]). Two deaths were judged by the investigators to be potentially treatment-related (one due to liver dysfunction and one due to multiple organ failure). INTERPRETATION:Camrelizumab showed antitumour activity in pretreated Chinese patients with advanced hepatocellular carcinoma, with manageable toxicities, and might represent a new treatment option for these patients. FUNDING:Jiangsu Hengrui Medicine. 10.1016/S1470-2045(20)30011-5
    [Clinical efficacy and safety analysis of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma: a multicenter retrospective study]. Yuan G S,He W M,Hu X Y,Li Q,Zang M Y,Cheng X,Huang W,Ruan J,Wang J J,Hou J L,Chen J Z Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology To analyze the clinical efficacy and safety of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma (HCC). Ninety-four cases with mid-and advanced-stage HCC who received camrelizumab combined with apatinib as second-line treatment were enrolled. Routine blood test, blood biochemical indexes, tumor stage, tumor imaging characteristics, previous treatment strategies and other clinical data before treatment were documented. Imaging examination follow-up results and adverse reactions during treatment were followed up until the end of follow-up or loss of follow-up or death. Kaplan-Meier method was used to analyze the clinical efficacy. As of the last follow-up, 94 cases with mid-and advanced-stage HCC had received camrelizumab combined with apatinib as second-line treatment. Among them, 15 cases were lost to follow-up, 31 cases died, and 48 cases survived. The overall remission rate was 31.9%. The overall disease control rate was 71.3%. The median time to disease-free progression was 6.6 months. The median time to disease progression was not yet available. The 1-year cumulative survival rate was 62.3%. Grade 3 and above adverse reactions mainly included were thrombocytopenia (7.4%), abdominal pain (4.3%), active hepatitis (4.3%), leukopenia (4.3%), diarrhea (3.2%), hand-foot syndrome (3.2%). All adverse reactions were effectively controlled. Camrelizumab combined with apatinib can effectively prolong the survival period of patients with mid-and advanced-stage HCC, and it is well tolerated. 10.3760/cma.j.cn501113-20210329-00148
    Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase II clinical trial. Journal for immunotherapy of cancer OBJECTIVE:This study aimed to assess the efficacy and safety of camrelizumab plus apatinib in patients with resectable hepatocellular carcinoma (HCC) as neoadjuvant therapy. METHODS:Initially, 20 patients with HCC were screened and 18 patients with resectable HCC were enrolled in this open-label, single-arm, phase II clinical trial. Patients received three cycles of neoadjuvant therapy including three doses of camrelizumab concurrent with apatinib for 21 days followed by surgery. Four to 8 weeks after surgery, patients received eight cycles of adjuvant therapy with camrelizumab in combination with apatinib. Major pathological reactions (MPR), complete pathological reactions (pCR), objective response rate (ORR), relapse-free survival (RFS), and adverse events (AE) were assessed. In addition, cancer tissue and plasma samples were collected before and after treatment, and genetic differences between responding and non-responding lesions were compared by tumor immune microenvironment (TIME) analysis, circulating tumor DNA (ctDNA) analysis and proteomics analysis. RESULTS:In 18 patients with HCC who completed neoadjuvant therapy, 3 (16.7%) and 6 (33.3%) patients with HCC reached ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST criteria, respectively. Of the 17 patients with HCC who received surgical resection, 3 (17.6%) patients with HCC reported MPR and 1 (5.9%) patient with HCC achieved pCR. The 1-year RFS rate of the enrolled patients was 53.85% (95% CI: 24.77% to 75.99%). Grade 3/4 AEs were reported in 3 (16.7%) of the 18 patients, with the most common AEs being rash (11.1%), hypertension (5.6%), drug-induced liver damage (5.6%), and neutropenia (5.6%) in the preoperative phase. The 289 NanoString panel RNA sequencing showed that TIME cell infiltration especially dendritic cells (DCs) infiltration was better in responding tumors than in non-responding tumors. Our results of ctDNA revealed a higher positive rate (100%) among patients with HCC with stage IIb-IIIa disease. When comparing patients with pCR/MPR and non-MPR, we observed more mutations in patients who achieved pCR/MPR at baseline (6 mutations vs 2.5 mutations, p=0.025). Patients who were ctDNA positive after adjuvant therapy presented a trend of shorter RFS than those who were ctDNA negative. Proteomic analysis suggested that abnormal glucose metabolism in patients with multifocal HCC might be related to different sensitivity of treatment in different lesions. CONCLUSION:Perioperative camrelizumab plus apatinib displays a promising efficacy and manageable toxicity in patients with resectable HCC. DCs infiltration might be a predictive marker of response to camrelizumab and apatinib as well as patients' recurrence. ctDNA as a compose biomarker can predict pathological response and relapse. Abnormal glucose metabolism in patients with multifocal HCC may be related to different sensitivity of treatment in different lesions. TRIAL REGISTRATION NUMBER:NCT04297202. 10.1136/jitc-2022-004656
    Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Xu Jianming,Shen Jie,Gu Shanzhi,Zhang Yun,Wu Lihua,Wu Jian,Shao Guoliang,Zhang Yanqiao,Xu Li,Yin Tao,Liu Jingfeng,Ren Zhenggang,Xiong Jianping,Mao Xianhai,Zhang Ling,Yang Jiayin,Li Lequn,Chen Xiaoming,Wang Zhiming,Gu Kangsheng,Chen Xi,Pan Zhanyu,Ma Kuansheng,Zhou Xinmin,Yu Zujiang,Li Enxiao,Yin Guowen,Zhang Xiao,Wang Shuni,Wang Quanren Clinical cancer research : an official journal of the American Association for Cancer Research PURPOSE:We assessed the efficacy and safety of camrelizumab [an anti-programmed death (PD-1) mAb] plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS:This nonrandomized, open-label, multicenter, phase II study enrolled patients with advanced HCC who were treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received intravenous camrelizumab 200 mg (for bodyweight ≥50 kg) or 3 mg/kg (for bodyweight <50 kg) every 2 weeks plus oral apatinib 250 mg daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) per RECIST v1.1. RESULTS:Seventy patients in the first-line setting and 120 patients in the second-line setting were enrolled. As of January 10, 2020, the ORR was 34.3% [24/70; 95% confidence interval (CI), 23.3-46.6] in the first-line and 22.5% (27/120; 95% CI, 15.4-31.0) in the second-line cohort per IRC. Median progression-free survival in both cohorts was 5.7 months (95% CI, 5.4-7.4) and 5.5 months (95% CI, 3.7-5.6), respectively. The 12-month survival rate was 74.7% (95% CI, 62.5-83.5) and 68.2% (95% CI, 59.0-75.7), respectively. Grade ≥3 treatment-related adverse events (TRAE) were reported in 147 (77.4%) of 190 patients, with the most common being hypertension (34.2%). Serious TRAEs occurred in 55 (28.9%) patients. Two (1.1%) treatment-related deaths occurred. CONCLUSIONS:Camrelizumab combined with apatinib showed promising efficacy and manageable safety in patients with advanced HCC in both the first-line and second-line setting. It might represent a novel treatment option for these patients.. 10.1158/1078-0432.CCR-20-2571
    Late combination of transarterial chemoembolization with apatinib and camrelizumab for unresectable hepatocellular carcinoma is superior to early combination. Ju Shuguang,Zhou Chen,Hu Junwen,Wang Yingliang,Wang Chaoyang,Liu Jiacheng,Yang Chongtu,Huang Songjiang,Li Tongqiang,Chen Yang,Bai Yaowei,Yao Wei,Xiong Bin BMC cancer OBJECTIVE:The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it. METHODS:In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS. RESULTS:A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8-30.5 months) and the median PFS was 15.7 months (95% CI: 14.7-16.6 months). The ORR was 58.8% (95% CI: 47.2-69.6) and DCR reached 81.2% (95% CI: 71.0-89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060-0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184-0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed. CONCLUSION:TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination. 10.1186/s12885-022-09451-1
    Efficacy of Drug-Eluting Beads Transarterial Chemoembolization Plus Camrelizumab Compared With Conventional Transarterial Chemoembolization Plus Camrelizumab for Unresectable Hepatocellular Carcinoma. Ren Yanqiao,Guo Yusheng,Chen Lei,Sun Tao,Zhang Weihua,Sun Bo,Zhu Licheng,Xiong Fu,Zheng Chuansheng Cancer control : journal of the Moffitt Cancer Center OBJECTIVES:The purpose of this study was to compare the efficacy and safety of drug-eluting beads transarterial chemoembolization plus camrelizumab (D-TACE-C) with conventional transarterial chemoembolization plus camrelizumab (C-TACE-C) in the treatment of patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS:This was a retrospective study that evaluated the consecutive medical records of patients with unresectable HCC who had undergone D-TACE-C or C-TACE-C from April 2020 to August 2021. Efficacy of treatment was evaluated using tumor response, progression-free survival (PFS) and survival rates. The adverse events were recorded. RESULTS:A total of 54 patients were included in this study, including 27 patients who had received D-TACE-C treatment, and 27 patients who had received C-TACE-C treatment. The median PFS and DCR in the D-TACE-C group were significantly longer than those for the C-TACE-C group (PFS: 10 vs. 3 months, P=.017; DCR: 70.4% vs. 40.7%, P = .028). Cox regression analysis showed that D-TACE-C was the only protective factor for PFS. The 6-month and 12-month survival rates in D-TACE-C group and C-TACE-C group were 85.2% versus 79.4% (P = .646) and 65.2% versus 65.1% (P = .903), respectively. Reactive cutaneous capillary endothelial proliferation was the most common adverse event associated with the treatment. There was no significant difference in the adverse events related to TACE and camrelizumab between the two groups. No treatment-related deaths occurred in this study. CONCLUSIONS:D-TACE-C is a safe and well-tolerated treatment, and may produce better PFS and tumor response in patients with unresectable HCC than C-TACE-C. 10.1177/10732748221076806
    Transarterial chemoembolization combined with camrelizumab for recurrent hepatocellular carcinoma. Guo Yusheng,Ren Yanqiao,Chen Lei,Sun Tao,Zhang Weihua,Sun Bo,Zhu Licheng,Xiong Fu,Zheng Chuansheng BMC cancer PURPOSE:To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection. PATIENTS AND METHODS:R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events. RESULTS:Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs. CONCLUSION:Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC. 10.1186/s12885-022-09325-6
    Effect of camrelizumab plus transarterial chemoembolization on massive hepatocellular carcinoma. Clinics and research in hepatology and gastroenterology OBJECTIVE:To investigate the efficacy of camrelizumab plus transarterial chemoembolization (TACE) on massive hepatocellular carcinoma (HCC) patients. METHODS:A total of 92 cases with massive HCC from October 2019 to January 2021 were prospectively enrolled and randomly divided into the study group (n = 46) and the control group (n = 46). The control group received TACE while the study group were treated with camrelizumab plus TACE. The primary end points were clinical efficacy and adverse events. And the secondary end points were liver function, and alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) levels before and after treatment. RESULTS:All participants were followed-up for 7 to 24 months, with a median of 12 months. Patients in the study group received TACE for 1-3 times, with an average of (2.01 ± 0.09) times, while patients in the control group receive TACE for 2-4 times, with an average of (3.78 ± 0.12) times, and the control group received significantly more TACEs (χ = 5.518, P = 0.019). During the follow-up, the response rate and disease control rate of the study group were significantly higher than those of the control group (χ = 5.518, P = 0.019; χ = 4.467, P = 0.041). Before treatment, the levels of total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP), CEA, and CA19-9 were comparable between the groups (P > 0.05). After treatment, the levels of TBIL, ALT, AST, AFP, CEA, and CA19-9 decreased, and the above indicators in the study group were significantly lower than those in the control group (P < 0.05). All patients showed transient liver damage, vomiting, nausea, fever and abdominal pain after surgery, and their symptoms were relieved after symptomatic treatment. Adverse events occurred in 9 cases in the study group, and 3 cases in the control group (χ = 3.419, P = 0.064). CONCLUSION:Compared with TACE alone, camrelizumab plus TACE treatment can significantly improve the liver function of patients with massive HCC and enhance the treatment effect, which is worthy of clinical promotion. 10.1016/j.clinre.2021.101851