Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

Xin, Yujing; Cao, Fei; Yang, Hongcai; Zhang, Mengjie; Chen, Yi; Cao, Xiaojing; Zhou, Xiang; Li, Xiao; Zhou, Jinxue

doi:10.3389/fimmu.2022.929141

Cited by 25 publications

(28 citation statements)

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“…In addition, a patient had gastrointestinal haemorrhage, which was successfully treated via endoscopic haemostasis. The incidence of grade-3 and -4 AEs was significantly higher in this study than in previous studies ( 14 , 35 ). This increase may be attributed to the inclusion of adverse reactions related to the process of perfusion therapy, such as abdominal pain and fever, in this study.…”

Section: Discussioncontrasting

confidence: 80%

“…HAIC is more effective than TACE in patients with a high tumour burden ( 10 , 32 , 33 ). The combination of HAIC and molecular targeted therapy can increase the tumour regression rate and improve prognosis ( 13 , 14 ). The findings of this study are similar to those of previous related studies.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with sorafenib monotherapy, combination therapy with sorafenib and FOLFOX-HAIC can improve the objective response rate (ORR) and OS of patients with HCC ( 12 , 13 ). In addition, the combination of HAIC, anti-PD-1-based immunotherapy and molecularly targeted agents may improve patient outcomes ( 14 , 15 ). However, relevant previous studies reporting on the abovementioned combination therapeutic strategies had a limited number of participants, which limits the external validation of the results.…”

Section: Introductionmentioning

confidence: 99%

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Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study

Zhang

Liu

et al. 2023

Front. Immunol.

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BackgroundMolecular targeted therapy combined with immunotherapy significantly improves the prognosis of patients with advanced liver cancer. Additionally, hepatic arterial infusion chemotherapy (HAIC) can improve the prognosis of patients with advanced liver cancer. This real-world study aimed to evaluate the clinical efficacy and safety of HAIC combined with molecular targeted therapy and immunotherapy in the treatment of primary unresectable hepatocellular carcinoma (uHCC).MethodsA total of 135 patients with uHCC were enrolled in this study. Progression-free survival (PFS) was the primary endpoint. The efficacy of the combination therapy was assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Overall survival (OS), adverse events (AEs) and surgical conversion rate were the secondary endpoints. Univariate and multivariate Cox regression analyses were performed to examine independent prognostic factors. For sensitivity analysis, inverse probability weighting (IPW) was used to balance the influence of the tested confounding factors between groups to verify the robustness of conversion surgery for survival benefits. The E-values were estimated to assess robustness to unmeasured confounders.ResultsThe median number of therapies was three. Approximately 60% of the patients had portal vein tumour thrombosis (PVTT). The most common targeted drugs were lenvatinib and bevacizumab, whereas the most common immunotherapy drug was sintilimab. The overall objective response rate (ORR) was 54.1%, and the disease control rate (DCR) was 94.6%. A total of 97 (72%) patients experienced AEs of grades 3–4. Fatigue, pain and fever were the most common symptoms of grade 3-4 AEs. The median PFS was 28 months and 7 months in the successful and unsuccessful conversion groups, respectively. The median OS was 30 months and 15 months in the successful and unsuccessful conversion groups, respectively. Successful conversion surgery, sex, hapatic vein invasion, BCLC stage, baseline tumour size, AFP levels and maximum therapeutic response were independent prognostic factors for PFS. Successful conversion surgery, number of interventions, hapatic vein invasion and total bilirubin levels were independent prognostic factors for OS. After IPTW, no standardised differences exceeding 0.1 were found. IPW-adjusted Kaplan–Meier curves showed that successful conversion surgery was an independent prognostic factor for both PFS and OS. The E-values of successful conversion surgery were 7.57 and 6.53 for OS and PFS, respectively, which indicated a relatively robust impact of successful conversion surgery on the prognosis of patients.ConclusionPatients with primary uHCC undergoing HAIC combined with immunotherapy and molecular targeted therapy have a higher tumour regression rate and the side effects are manageable. Patients undergoing surgery after combination therapy have survival benefits.

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Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study

Zhang

Liu

et al. 2023

Front. Immunol.

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“…HCC is among the five most prevalent cancers, and primary liver cancer ranges from 70–90%, making it the third major factor contributing to the extremely high mortality rate from cancer. In China, the incidence rate and mortality rate of liver cancer in malignant tumors rank fourth and second respectively, with a 5-year survival rate of merely 18% . Presently, various therapies are available for the treatment of HCC.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20

Su,

Lu,

et al. 2023

ACS Pharmacol. Transl. Sci.

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“…However, this is an interesting topic that has recently yielded favorable data, so further evaluation of HAIC in combination with the newer drugs is warranted. 3 Second, treatment-associated adverse events were more common in the HAIC group than in the sorafenib group. Most grade 3 or 4 adverse events were hematologic or portrelated events, which are mostly manageable.…”

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confidence: 96%

Comments on Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Reply

et al. 2023

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We appreciate the letter from Deng and colleagues regarding our study. They raised several questions related to the treatment of hepatocellular carcinoma with sorafenib or hepatic arterial infusion chemotherapy (HAIC). 1 First, they were curious about combination therapies. As we described in the combination and second-line therapy section, patients in the HAIC group more frequently (68%) received combination such as transarterial chemolipiodolization (15.3%), radiotherapy (26.3%), or both therapies (23.7%) as well as radiotherapy plus percutaneous ethanol injection (2.6%). Among the patients in the sorafenib group, only 17% received combination therapy using transarterial chemolipiodolization (5.7%) and radiotherapy (11.4%). To prevent ischemic insults to the liver in the presence of portal vein tumor thrombosis, we chose transarterial chemolipiodolization for patients needing local tumor control. 2 However, overall survival or time to progression was not different between the monotherapy and combination therapy groups. During the study period, as there was no approved immune-oncologic agent, we did not have a chance to evaluate the combination of HAIC with immunotherapies such as atezolizumab plus bevacizumab. However, this is an interesting topic that has recently yielded favorable data, so further evaluation of HAIC in combination with the newer drugs is warranted. 3 Second, treatment-associated adverse events were more common in the HAIC group than in the sorafenib group. Most grade 3 or 4 adverse events were hematologic or portrelated events, which are mostly manageable. 1 Regarding the underlying liver function and performance, one-third had Child-Pugh class B and another one-third showed Eastern Cooperative Oncology Group grade 2 or 3 status in our study. These patients were associated with worse survival than those with well-preserved liver function and performance status as Deng and colleagues indicated. However, we cannot exclude these patients from the treatment in the real-life setting as their survival is too short with supportive care only. In our study, compared with sorafenib, HAIC showed trends of benefit in overall survival in patients with Child-Pugh B liver function (5.9 months vs 15.3 months for Child-Pugh 7 and 3.4 months vs 5.9 months for Child-Pugh 8 or 9) and performance status 3 (0.8 months vs 6.3 months, respectively). 1 However, there were no statistical differences, suggesting further studies with lager number of patients are needed in these subgroups of the population.Third, although we used cisplatin and 5-fluorouracil for HAIC, there are reports of combining new cytotoxic agents such as oxaliplatin. 4,5 We appreciate the suggestion of performing HAIC using FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin), which significantly improved overall survival over sorafenib. Furthermore, improved local tu-

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Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

Cited by 25 publications

References 50 publications

Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study

Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study

MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20

Comments on Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Reply

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