scholarly journals Real-world outcome of immune checkpoint inhibitors for advanced hepatocellular carcinoma with macrovascular tumor thrombosis

2021 ◽  
Author(s):  
Hong-Ming Tsai ◽  
Meng-Zhi Han ◽  
Yih-Jyh Lin ◽  
Ting-Tsung Chang ◽  
Chiung-Yu Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Response Rate ◽  
Objective Response ◽  
Similar Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Vascular Response ◽  
Tumor Thrombosis ◽  
Tumor Thrombi

AbstractProgrammed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting. Among the 110 patients with unresectable HCC treated with PD-1 inhibitors, 34 patients with vascular metastases in the portal vein and inferior vena cava were retrospectively compared with 34 patients without tumor thrombi. The vascular response and its effect on survival were assessed. Predictors of survival were identified using multivariate analysis. Among patients achieving objective response, those with and without thrombi exhibited similar response to immunotherapy and comparable survival. Among the 34 patients with tumor thrombi, including 13 receiving PD-1 inhibitors alone and 21 receiving it in combination with tyrosine kinase inhibitors, the median overall survival was 8.9 months (95% confidence interval 3.2–12.6). The objective response rate of vascular metastasis was 52.9%, and vascular responders had a significantly longer survival than did non-responders (11.1 vs 3.9 months). Failure to obtain a vascular response correlated significantly with increased post-treatment Child–Pugh score or class. Multivariate analysis showed that vascular response was a significant positive factor for longer overall survival. Treatment-related grade 3/4 adverse events occurred in 3 (8.8%) of the patients with tumor thrombi. Immunotherapy with PD-1 inhibitors may be a feasible treatment option for HCC with tumor thrombi owing to the high response rate of tumor thrombi and favorable survival outcomes.

Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15678-e15678
Author(s):  
Beom Kyung Kim ◽  
Do Young Kim ◽  
Hye Jin Choi ◽  
Seung-Hoon Beom ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Objective Response Rate ◽  
Median Overall Survival ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Sorafenib Treatment

e15678 Background: Patients with advanced hepatocellular carcinoma (HCC) have a particularly poor prognosis of the median overall survival of less than 12 months. Even though sorafenib has been approved for treating advanced stage HCC, the unsatisfactory objective response rate still remain unresolved. In the current study, we aimed to evaluate the efficacy and safety of localized concurrent chemoradiotherapy (CCRT) followed by sequential sorafenib treatment for advanced hepatocellular carcinoma. Methods: This study is an ongoing, phase II trial. Patients with advanced HCC not amenable for curative treatments were eligible. In the course of radiotherapy for 5 weeks, hepatic arterial infusion of 5-fluorouracil (500mg/day) via implanted port was applied during the first 5 days and the last 5 days of radiotherapy. Four weeks after localized CCRT, sorafenib (400mg bid) was maintained. The primary endpoint was overall survival. Results: A total of 47 patients were enrolled. After the completion of localized CCRT, the objective response rate was 31.9%. During the overall treatment course, the objective response rate was 46.8% respectively. Overall, 7 patients (14.9%) underwent curative resection or transplantation after down-staging. The median overall survival was 18.4 months and the progression-free survival was 6.8 months. Adverse events were predictable and manageable with conservative care. Conclusions: Localized CCRT followed by sequential sorafenib treatment in patients with advanced HCC showed significant activity and good tolerability. Furthermore, such a treatment modality, when compared to the use of sorafenib alone, might provide the additional therapeutic benefit through initial tumor reduction, allowing curative treatment after down-staging in 14.9% of patients, Further randomized trial should be required to make the more robust evidence. Clinical trial information: NCT02425605.

scholarly journals Network meta-analysis of nivolumab plus ipilimumab in the second-line setting for advanced hepatocellular carcinoma

2021 ◽  
Author(s):  
Neehar D Parikh ◽  
Alexander Marshall ◽  
Keith A Betts ◽  
Jinlin Song ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Objective Response Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Credible Interval ◽  
Hazard Ratio ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line

Aims: To compare the efficacy of nivolumab 1 mg/kg + ipilimumab 3 mg/kg with regorafenib 160 mg, cabozantinib 60 mg and nivolumab 3 mg/kg monotherapy for second-line treatment of advanced hepatocellular carcinoma. Materials & methods: Indirect comparison using network meta-analysis and propensity score weighting. Results: Nivolumab 1 mg/kg + ipilimumab 3 mg/kg had significantly higher objective response rate (median 31.2% [95% credible interval: 19.6–44.5%]) than cabozantinib (4.2% [2.0–6.5%]) and regorafenib (4.8% [1.1–8.3%]), and significantly longer overall survival (cabozantinib: hazard ratio: 0.46 [95% credible interval: 0.27–0.79]; regorafenib: 0.56 [0.32–0.97]). Nivolumab 1 mg/kg + ipilimumab 3 mg/kg had significantly better objective response rate (difference 21.0% [4.5–37.5%]) and overall survival (hazard ratio: 0.58 [0.35–0.96]) than nivolumab monotherapy. Conclusion: Nivolumab 1 mg/kg + ipilimumab 3 mg/kg had a superior efficacy versus cabozantinib 60 mg, regorafenib 160 mg and nivolumab 3 mg/kg monotherapy as second-line therapy for advanced hepatocellular carcinoma.

scholarly journals Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

2021 ◽  
Author(s):  
Osman Öcal ◽  
Kerstin Schütte ◽  
Juozas Kupčinskas ◽  
Egidijus Morkunas ◽  
Gabija Jurkeviciute ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Post Hoc Analysis ◽  
Y90 Radioembolization ◽  
Baseline Values ◽  
Post Hoc

Abstract Purpose To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Methods A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. Results Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9–8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2–4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22–7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02–4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011). Conclusion IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.

scholarly journals Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1272 ◽  
Author(s):  
Laura Marconato ◽  
Silvia Sabattini ◽  
Giorgia Marisi ◽  
Federica Rossi ◽  
Vito Ferdinando Leone ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Safety Profile ◽  
Median Overall Survival ◽  
Response Rate ◽  
Treatment Options ◽  
Objective Response ◽  
Metronomic Chemotherapy ◽  
Time To Progression ◽  
Activity Data

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.

scholarly journals Efficacy of Stereotactic Body Radiotherapy for Recurrent or Residual Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Erhua Yao ◽  
Jinghong Chen ◽  
Xiaofang Zhao ◽  
Yinyan Zheng ◽  
Xianheng Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Stereotactic Body Radiotherapy ◽  
Palliative Treatment ◽  
Median Overall Survival ◽  
Transcatheter Arterial Chemoembolization ◽  
Response Rate ◽  
Objective Response ◽  
Overall Survival Rate ◽  
Arterial Chemoembolization

Aim. To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy (SBRT) for patients with recurrent or residual hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). Methods. Between June 2008 and July 2015, thirty-three patients with HCC were treated by SBRT. There were 63 lesions in 33 patients. A total dose of 39–45 Gy/3–5 fractions was delivered to the 70–80% isodose line. Results. Objective response rate (CR + PR) was 84.8% at 6 months. The overall survival rate was 87.9%, 75.8%, 57.6%, and 45.5% at 6, 12, 18, and 24 months, respectively. Median overall survival was 19 months. At 3 months, AFP decreased by more than 75% in 51.5% of patients (17/33). Overall survival was significantly different (P<0.001) between the group of patients for whom AFP decreased more than 75% and the group for whom AFP decreased by less than 75%. The AFP-negative rate was 48.5% (16/33) after 6 months. Eight patients (24.2%) had grade 1-2 transient fatigue, and 11 patients (33.3%) had grade 1-2 gastrointestinal reactions within 1 month. Conclusion. SBRT is a promising noninvasive and palliative treatment with acceptable toxicity for recurrent or residual HCC after TACE.

Experience with Sorafenib in 3 Hospitals in Sao Paulo

2018 ◽  
Vol 17 (5) ◽  
pp. 0-10
Author(s):  
Rogério Camargo-Pinheiro-Alves ◽  
Daniele E. Viera-Alves ◽  
Arthur Malzyner ◽  
Otavio Gampel ◽  
Thaisa de F. Almeida-Costa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Complex Disease ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Treatment Strategies ◽  
Sao Paulo ◽  
Advanced Hepatocellular Carcinoma ◽  
São Paulo ◽  
Sorafenib Therapy

Introduction and aim. Sorafenib has been the standard of care for first-line treatment of advanced hepatocellular carcinoma, a complex disease that affects an extremely heterogenous population. Thereby requiring multidisciplinary individualized treatment strategies that match the disease characteristics and the patients’ specific needs. Material and methods. Data for 175 patients who received sorafenib for hepatocellular carcinoma in three different hospitals in Sao Paulo, Brazil over a span of nine years were retrospectively analyzed. Results. The median age was 62 years. Percentages of patients with Child-Pugh A, B and C liver cirrhosis were 61%, 31% and 5%, respectively. Approximately half of the patients had Barcelona Clinic Liver Cancer stage B disease, and the other half had stage C. The median treatment duration was 253 days. Sorafenib dose was reduced to 400 mg/day in 41% of the patients due to toxicity. Overall objective response rate as per Response Evaluation Criteria in Solid Tumors and its modified version was 39%. Patients who received transarterial chemoembolization (TACE) at any point during sorafenib therapy were significantly more likely to experience an objective response. After a median follow-up of 339 days, the median overall survival was 380 days. Child-Pugh cirrhosis, tumor response and concomitant chemoembolization were independent prognostic factors for overall survival in multivariate analysis. Conclusion. Our results suggest that, in experienced hands, sorafenib therapy may benefit carefully selected hepatocellular carcinoma patients for whom other therapies are initially contraindicated, including those patients with Child-Pugh B liver function and those patients who are subsequently treated with concomitant TACE.

scholarly journals Transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil versus transarterial chemoembolization using doxorubicin for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective analysis

2017 ◽  
Vol 9 (10) ◽  
pp. 615-626 ◽  
Author(s):  
Sung Won Lee ◽  
Hae Lim Lee ◽  
Nam Ik Han ◽  
Jung Hyun Kwon ◽  
Soon Woo Nam ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Rate ◽  
Tumor Response ◽  
Response Rate ◽  
Portal Vein Tumor Thrombosis ◽  
Advanced Stage ◽  
Overall Survival Rate ◽  
Tumor Thrombosis ◽  
Transarterial Infusion

Background: More than one-third of hepatocellular carcinoma (HCC) patients are diagnosed at advanced stage with portal vein tumor thrombosis (PVTT) or extrahepatic metastasis. However, the outcomes of current therapeutic approaches are unsatisfactory. As a novel therapeutic strategy for unresectable HCC with PVTT, we analyzed the outcomes of transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil (TAC-ECF) and compared its therapeutic effects and toxicity with transarterial chemoembolization (TACE) using doxorubicin (DOX). Methods: A total of 540 consecutive HCC patients who received TACE at the Catholic Medical Center between January 2007 and November 2013 were enrolled. Of these patients, we retrospectively analyzed 129 Barcelona clinic liver cancer stage C HCC patients with PVTT who received either TAC-ECF or TACE using DOX. Results: The objective tumor response rate was higher in the TAC-ECF group, with 31.3% objective response rate after TAC-ECF compared to 10% after DOX treatment ( p = 0.004). Median follow-up period was 7 months (range, 1–57 months). The overall survival rate was also significantly higher in the TAC-ECF group compared to the DOX group (median 9.3 versus 4.6 months, p < 0.0001). Multivariate analysis revealed that TAC-ECF and extrahepatic metastasis were independent predictive factors for overall survival ( p < 0.0001 and p = 0.002 respectively). No serious adverse effects developed in both groups. Conclusions: TAC-ECF therapy was tolerable and showed higher overall survival rate and tumor response compared to the conventional TACE DOX in advanced stage HCC patients with PVTT. Therefore, TAC-ECF may be considered as an effective treatment option for patients with unresectable HCC.

scholarly journals Objective Response by mRECIST is an Independent Prognostic Factor for overall Survival in Hepatocellular Carcinoma in SILIUS Trial

2019 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Yasutaka Chiba ◽  
Sadahisa Ogasawara ◽  
Shuntaro Obi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Objective Response ◽  
Independent Prognostic Factor ◽  
Combination Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Group ◽  
Landmark Analyses

Background In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and overall survival (OS) in the sorafenib group, in the combination group and in all patients in the SILIUS trial. Methods Association between objective response and OS in patients treated with sorafenib (n=103), combination (n=102) and all patients (n=205) were analyzed. The median OS of responders was compared with that of non-responders. Landmark analyses were performed according to objective response at several fixed time points, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with objective response as a time-dependent covariate, with other prognostic factors was performed. Results In the sorafenib group, OS of responders (n = 18) was significantly better than that of non-responders (n = 78) (p &lt; 0.0001), where median OS was 27.2 (95% CI, 16.0&ndash;not reached) months for responders and 8.9 (95% CI, 6.5&ndash;12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 (p=0.0330), 0.37 (p=0.0053), and 0.36 (p=0.0083), respectively. Objective response was an independent predictor of OS based on unstratified Cox regression analyses. In the all patients and the combination group, similar results were obtained. Conclusion In the SILIUS trial, objective response was an independent prognostic factor for OS in patients with HCC.

The use of cabozantinib in advanced hepatocellular carcinoma (HCC): Hong Kong multi-center experience.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 316-316
Author(s):  
Yawen Dong ◽  
Thomas Wai-Tong Leung ◽  
Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hong Kong ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Real Life ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

316 Background: In the phase III CELESTIAL trial, cabozantinib showed significant improvement in overall survival with good tolerability in advanced HCC population. We aimed to evaluate the efficacy, survival and tolerability of cabozatinib in advanced hepatocellular carcinoma (HCC) patients in a real life setting. Methods: Between February 2018 and October 2019, consecutive advanced HCC patients who received cabozatinib alone or in combination at University of Hong Kong Health System hospitals were analysed. Cabozantinib was administered at 60 mg continuously daily. Objective response rate (ORR), time-to-progression (TTP), overall survival (OS), and tolerability were evaluated. Results: Overall, 22 patients were included. The median age was 57.1 years (range 48.5-58.6). All patients except one were hepatitis B carriers. More than 80% of the patients had underlying Child-Pugh A cirrhosis. Most patients had metastatic disease (95.5%). More than 70% of patients received cabozantinib beyond second-line, and most of the patients had prior exposure to tyrosine kinase inhibitor (TKI) and/or immunotherapy. The median time from the start of first-line systemic treatment to the start of cabozantinib was 11.2 months. Cabozantinib was administered to 11 patients (50%) as single agent, while the other half received cabozantinib in combination with mostly immune checkpoint inhibitors. The median follow-up was 7.6 months. The table below shows the ORR. The overall median TTP and OS were 4.2 and 8.90 months, respectively. Interestingly, among those who received single agent cabozantinib, the median OS was 5.36 months in contrast to 12.32 months in the patients received combination. Overall, 90.9% of patients experienced treatment related adverse events (TRAEs) with transient liver function occurred in nearly 50% patients. Nevertheless, Grade 3/4 TRAEs was only 12%. Conclusions: Our present study showed that the use of cabozatinib in advanced HCC patients had good anti-tumour activity and survival benefits with acceptable toxicity profile. [Table: see text]

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