scholarly journals Surgical Conversion for Initially Unresectable Locally Advanced Hepatocellular Carcinoma Using a Triple Combination of Angiogenesis Inhibitors, Anti-PD-1 Antibodies, and Hepatic Arterial Infusion Chemotherapy: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinliang Zhang ◽  
Xihao Zhang ◽  
Han Mu ◽  
Ge Yu ◽  
Wenge Xing ◽  
...  

BackgroundRecent research has shown that selected patients with initially unresectable hepatocellular carcinoma (HCC) are able to achieve conversion to resectable disease through systemic or local therapy. Combination regimens comprised of drugs with different mechanisms of action have shown better outcomes than single-drug or single-approach-based treatments; however, to date, combination regimens investigated as part of conversion therapy strategies have been two drug combinations with reported issues of relatively low surgical conversion and objective response rates. In this study, we investigated the efficacy and safety of triple combination therapy with angiogenesis inhibitors, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy for surgical conversion of advanced HCC.MethodsThis was a single-center, retrospective, single-arm study of patients with unresectable HCC who received at least one cycle of triple combination therapy with an oral anti-angiogenic drug, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy between August 2019 and August 2020. Endpoints included the overall response rate (ORR), surgical conversion rate, time to response and safety. Treatment response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1.ResultsIn total, 34 patients were included in this study, of whom 25 completed treatment evaluation. The best ORR was 96.0% (24/25); 48.0% (n = 12) had a complete response, 48.0% (n = 12) had a partial response, and 4.0% (n = 1) had stable disease. The median time to response was 50.5 (95% CI, 31.02–64.00) days and the surgical conversion rate was 60% (15/25). Of the 25 patients, 56.0% (n = 14) received surgical resection and 28.0% (n = 7) had a pathologic complete response. Toxic side effects were manageable.ConclusionA triple combination therapy regimen of angiogenesis inhibitors, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy showed significant therapeutic effect with an extremely high surgical conversion rate in patients with initially unresectable HCC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16124-e16124
Author(s):  
Ti Zhang ◽  
Jinliang Zhang ◽  
Xihao Zhang ◽  
Han Mu ◽  
Ge Yu ◽  
...  

e16124 Background: The effects of single-drug therapy for the systemic treatment of advanced unresectable hepatocellular carcinoma (HCC) remain unsatisfactory, promoting the emergence of multi-drug and combination therapies. Here we assess the safety and efficacy of a triple combination therapy for treating advanced HCC. Methods: This single-center retrospective study included patients with unresectable HCC treated with triple combination therapy comprising angiogenesis inhibitors (oral apatinib 250 mg/day, lenvatinib 8 mg/day, or sorafenib 400 mg BID), anti-programmed cell death 1 antibodies (iv camrelizumab or sintilimab, 200 mg every 3 weeks), and hepatic arterial infusion chemotherapy (FOLFOX every 4–8 weeks). Eligible patients had completed at least one cycle of therapy and had an imaging assessment. Treatment-related adverse events (TRAEs) were assessed according to the Common Terminology Criteria for Adverse Events. Efficacy data were summarized according to modified RECIST (mRECIST) and RECIST v1.1. Results: Of 34 patients who received triple combination therapy, 25 (19 men and 6 women; median age: 59 years [range: 49–78]) had an imaging assessment. TRAEs were manageable; 28.0% of patients experienced grade 3–4 TRAEs. Efficacy outcomes are summarized in the Table. The objective response rate was 96.0% (mRECIST), the median time to response was 50.5 days (95% CI: 31.02–64.00) and the surgical conversion rate was 56%, indicating a robust therapeutic effect. Overall, 12 patients (48.0%) achieved a complete response (CR), 12 (48.0%) achieved a partial response, and one (4.0%) had stable disease (mRECIST). Fourteen patients (56.0%) underwent surgical resection, after which seven (28.0%) achieved a pathologic CR. After a median follow-up of 9.67 months, no cases of post-operative recurrence or metastasis emerged. Conclusions: Triple combination therapy had a robust therapeutic effect with a high surgical conversion rate in patients with advanced HCC. TRAEs were acceptable, and long-term efficacy is reasonably expected. Summary of efficacy outcomes (n = 25).[Table: see text]


Author(s):  
Qing Gou ◽  
Lingeng Wu ◽  
Wei Cui ◽  
Zhiqiang Mo ◽  
Dejin Zeng ◽  
...  

Abstract Objective To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). Methods We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. Results Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1–9.3) than in the control group (4.3 months, 95% CI: 3.6–5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1–16.5; control: 8.5 months, 95% CI: 7.6–9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. Conclusions Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. Key Points • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.


2021 ◽  
Vol 11 (4) ◽  
pp. 1882
Author(s):  
Takahiro Yamasaki ◽  
Issei Saeki ◽  
Yurika Kotoh-Yamauchi ◽  
Ryo Sasaki ◽  
Norikazu Tanabe ◽  
...  

Recent success of systemic therapeutic agents, including combination immunotherapy, could promote a change in the treatment strategy in patients with advanced hepatocellular carcinoma (HCC). Although hepatic arterial infusion chemotherapy (HAIC) is a treatment option for advanced HCC in Japan, it is not recommended by other guidelines. We discuss the clinical benefits of HAIC compared to sorafenib. The clinical benefits of HAIC are as follows: (1) even a patient with Child–Pugh B HCC (7 or 8 points) is a candidate for HAIC (2) Child–Pugh scores barely decline with the use of HAIC compared with sorafenib (3) HAIC is highly effective in patients with vascular invasion compared with sorafenib; and (4) survival in patients receiving HAIC may not be associated with skeletal muscle volume. In contrast, the disadvantages are problems related with the reservoir system. HAIC has clinical benefits in a subpopulation of patients without extrahepatic metastasis with Child–Pugh A HCC and vascular invasion (especially primary branch invasion or main portal vein invasion) or with Child–Pugh B HCC.


2021 ◽  
Vol 10 (4) ◽  
pp. 629
Author(s):  
Kei Moriya ◽  
Tadashi Namisaki ◽  
Hiroaki Takaya ◽  
Kosuke Kaji ◽  
Hideto Kawaratani ◽  
...  

Despite the availability of molecularly targeted agents for advanced hepatocellular carcinoma (aHCC), these are limited to compensated cirrhotic patients, and concerns about decreased hepatic functional reserve (HFR) and unknown adverse events, which may affect long-term survival, remain unaddressed. In this study, we enrolled 96 aHCC patients treated with bimonthly hepatic arterial infusion chemotherapy (B-HAIC) with cisplatin or sorafenib monotherapy (oral sorafenib 400 mg twice daily) not only to demonstrate its efficacy and significance but also to indicate preferable candidates by setting a response-related biomarker. Differences in treatment had no significant effect on overall survival (OS). The response rate in patients treated with B-HAIC was relatively higher than those treated with sorafenib. HFR was well maintained over the treatment course with B-HAIC, while it was significantly impaired with sorafenib. By employing multivariate analysis, we found negative trends between progression-free survival (PFS) periods and serum levels of alpha fetoprotein as well as des-gamma-carboxy prothrombin (DCP). In addition, a logistic regression analysis of the relationship between serum DCP levels and PFS periods over 420 days (14 months) showed that the PFS periods of patients with higher DCP was significantly shorter than those of patients with lower DCP (p = 0.02). Subsequently, the present study demonstrated the efficacy and safety of B-HAIC and identified a predictor of unpreferable patients. Based on these results, B-HAIC might be an alternative treatment after the implementation of new molecularly targeted therapies.


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