Efficacy and Safety of Raltitrexed‐based Transcatheter Arterial Chemoembolization for Intermediate and Advanced Hepatocellular Carcinoma: a Multicenter Real‐World Study

2021 ◽  
Author(s):  
Jiahui He ◽  
Hang Sun ◽  
Fei Li ◽  
Hao Yang ◽  
Minggeng Lou ◽  
...  
2021 ◽  
Author(s):  
Jian-Xu Li ◽  
Wen-Xiang Deng ◽  
Shi-Ting Huang ◽  
Xiao-Feng Lin ◽  
Mei-Ying Long ◽  
...  

Abstract Background: The combination of transcatheter arterial chemoembolization (TACE) plus sorafenib prolonged progression-free survival (PFS) and overall survival (OS) than sorafenib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of radiotherapy (RT) plus monoclonal antibody against programmed cell death 1 (anti-PD1) versus TACE plus sorafenib for patients with advanced HCC.Methods: Patients with advanced HCC who treated with RT plus anti-PD1 and TACE plus sorafenib were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety.Results: Between January 2018 to March 2021, 37 patients underwent RT plus anti-PD1 and 41 patients underwent TACE plus sorafenib. The baseline characteristics between the two groups were comparable. The ORR and DCR were significantly higher in the RT+PD1 group than the TACE plus sorafenib group according to RECIST 1.1 (54.05% vs 12.20%, P < 0.001; 70.27% vs 46.37%, P = 0.041; respectively) and according to mRECIST (56.76% vs 31.71%, P = 0.039; 70.27% vs 46.37%, P = 0.041; respectively). RT plus anti-PD1 provided significantly better PFS (HR, 0.51; 95% CI 0.30-0.86; p=0.017) than TACE plus sorafenib. Moreover, patients with RT plus anti-PD1 had significantly higher 3-, 6-, and 9-month OS rates than those with TACE plus sorafenib(97.3% vs 92.30%, P < 0.001; 91.89% vs 68.60%, P < 0.001; 75.5% vs 60.60%, P < 0.001; respectively). The median OS was more favorable 17.4 months for the RT+PD1 group and 11.9 months for the TACE plus sorafenib group. No treatment-related death was observed. Grade 3 or more treatment-related adverse events (TRAEs) occurred significantly less in patients in the RT+PD1 group than the TACE plus sorafenib group (29.7% vs 75.6%, p < 0.001), and all TRAEs were manageable.Conclusions: In this real-world study, RT plus anti-PD1 showed significantly promising efficacy and manageable safety than TACE plus sorafenib in patients with advanced HCC. Toxicities were manageable, with no unexpected safety signals. The study provides evidence on a new therapeutic method in the treatment of advanced HCC.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15504-e15504
Author(s):  
Wei Zhang ◽  
Zhiping Yan

e15504 Background: Effective options for patients with advanced hepatocellular carcinoma (HCC) are urgently needed. Studies have shown that combination of sorafenib with TACE could imorove survival for the treatment of locoregional HCCs. Apatinib is a novel and highly selective inhibitor of VEGFR2 tyrosine kinase. We were aiming to explore the efficacy and safety of apatinib combined with TACE in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. Methods: This was a single-center single-arm phase 2 study. The key inclusion criteria included: (1) Histologicaly and cytologicaly diagnosed as Hepatocellular carcinoma of the liver ( HCC ) and with at least one imaging examination of measurable lesions, CT or MR scan long diameter of tumor ≥ 10 mm. (2) BCLC B / C; (3) Progressed after at least twice TACE. Eligible pts received apatinib at 500 mg/day for a maximum after TACE 4-7 days, and TACE treatment was performed after 4 days of discontinuation of apatinib until unacceptable toxicity or tumor recurrence. The primary endpoint was time to progression (TTP), which was defined as the time from enrollment to disease progression. The secondary endpoint was overall survival (OS) and treatment safety. Results: From May 27, 2018 to Oct 12, 2019, 22 pts wereenrolled. 5 pts received TACE more than 5 times, and 17 pts received TACE within 4 times. For 20 evaluable pts, two pts achieved partial response (10%), and 13 patients achieved stable disease. The ORR and DCR were 10% and 75%, respectively. At the cutoff data of Nov 4, 2019, 5 pts were still on treatment. 16 recurrenced and 5 death occurred. The mTTP was 5.09 months (95% CI, 3.48-7.16), and the mOS was not reached. Treatment-related adverse events occurred in 12 pts (60%). Seven grade 3 or 4 adverse events were reported (35%), respectively wereascites (2), platelet count decrease (1), elevated ALT/AST (1), hypertension (1), proteinuria (1) and nausea (1). None of the treatment related AEs was fatal. Conclusions: Apatinib combined with TACE might be effective and tolerant in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. Clinical trial information: NCT03510416.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhaonan Li ◽  
Quanjing Chen ◽  
Wenguang Zhang ◽  
Guangyan Si ◽  
Jing Li ◽  
...  

Purpose. The goal of this study was to assess the clinical efficacy and safety of the arsenic trioxide (ATO)/lipiodol emulsion in the transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hepatocellular carcinoma (HCC). Methods. From December 2015 to February 2017, a total of 87 patients were consecutively enrolled and underwent ATO-TACE (aTACE) combined with apatinib in the treatment of advanced HCC. The treatment response and adverse events were assessed at the first month and third month after aTACE therapy. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events were also analyzed. Results. 87 patients (57 men; 30 women) were enrolled in the present study. Compared to that at the pre-aTACE examination, the levels of AST and ALT were elevated at the first week after procedure (65.84 U/L ± 22.93 U/L vs. 54.15 U/L ± 19.60 U/L, p = 0.032 ; 63.44 U/L ± 22.50 U/L vs. 51.60 U/L ± 13.89 U/L, p = 0.027 , respectively). Most of the adverse events were grade 1 or 2 according to National Cancer Institute Common Terminology Criteria for Adverse Event (CTCAE). Of the exception, 4 persons (2%) did have grade 3 hand-foot skin reactions, 1 (1%) had grade 3 diarrhea, 1 (1%) had grade 3 hypertension, and 3 (3%) had grade 3 proteinuria and forced to reduce the dose of apatinib by half. The survival analysis of the combination with aTACE and apatinib therapy found that the median PFS was 10.2 months (95% CI: 8.543–11.857), and the median OS was 23.300 months (95% CI: 20.833–25.767). Additionally, both univariate and multivariate Cox regression revealed that the tumor burden (≤50%) and the patients without portal vein tumor thrombus (PVTT) significantly impacted the patient’s PFS and OS and were related to better survival. Conclusion. aTACE combined with apatinib is a safe and promising treatment approach for patients with advanced HCC. Additionally, tumor burden (≤50%) and the patients without PVTT are associated with better PFS and OS.


Liver Cancer ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Yeonghak Bang ◽  
Neung Hwa Park ◽  
Jung Woo Shin ◽  
...  

Introduction/Objective: Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed. Methods: We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed. Results: Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1–6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8–16.5) months for patients treated with first-line lenvatinib (n = 57). With second- or later-line lenvatinib (n = 17), median PFS and OS were 4.1 (95% CI 3.1–5.1) and 6.4 (95% CI 5.1–7.7) months, respectively. In the Child-Pugh B group (n = 18), median PFS and OS were 2.6 (95% CI 0.6–4.6) and 5.3 (95% CI 2.0–8.5) months, respectively. The most common grade 3–4 toxicities were hyperbilirubinemia (n = 8; 8.7%), AST elevation (n = 6; 6.5%), and diarrhea (n = 5; 5.4%) across all study patients. Conclusions: In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.


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