scholarly journals Posttreatment after Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer ◽  
2021 ◽  
pp. 1-12
Author(s):  
Keisuke Koroki ◽  
Naoya Kanogawa ◽  
Susumu Maruta ◽  
Sadahisa Ogasawara ◽  
Yotaro Iino ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Objective Response ◽  
Lower Probability ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
First Line ◽  
Sorafenib Treatment ◽  
The Third ◽  
Third Line

<b><i>Background:</i></b> There is no standard posttreatment for patients with advanced hepatocellular carcinoma (HCC) in whom lenvatinib therapy has failed. This study aimed to investigate rates of migration to posttreatment after lenvatinib and to explore candidates for second-line agents in the patients with failed lenvatinib therapy. <b><i>Methods:</i></b> We retrospectively collected data on patients with advanced HCC who received lenvatinib as the first-line agent in 7 institutions. <b><i>Results:</i></b> Overall survival and progression-free survival (PFS) of 178 patients who received lenvatinib as the first-line agent were 13.3 months (95% confidence interval [CI], 11.5–15.2) and 6.7 months (95% CI, 5.6–7.8), respectively. Sixty-nine of 151 patients (45.7%) who discontinued lenvatinib moved on to posttreatment. The migration rates from lenvatinib to the second-line agent and from the second-line agent to the third-line agent were 41.7 and 44.4%, respectively. Based on multivariate analysis, response to lenvatinib (complete or partial response according to modified RECIST) and discontinuation of lenvatinib due to radiological progression, as well as male were associated with a significantly higher probability of migration to posttreatment after lenvatinib. On the other hand, alpha-fetoprotein levels of 400 ng/mL or higher was correlated with a significantly lower probability of migration to posttreatment after lenvatinib. Of 63 patients who received second-line systemic therapy, 53 (84.2%) were administered sorafenib. PFS, objective response rate (ORR), and disease control rate (DCR) for sorafenib treatment were 1.8 months (95% CI, 0.6–3.0), 1.8%, and 20.8%, respectively. According to the Cox regression hazard model, Child-Pugh class B significantly contributed to shorter PFS. PFS, ORR, and DCR of 22 patients who received regorafenib after lenvatinib in any lines were 3.2 months (range, 1.5–4.9 months), 13.6%, and 36.3%, respectively. Similarly, PFS, ORR, and DCR of 17 patients who received regorafenib after lenvatinib in the third-line (after sorafenib) were 3.8 months (range, 1.1–6.5 months), 17.6%, and 41.2%, respectively. <b><i>Conclusion:</i></b> Sorafenib may not be a candidate for use as a posttreatment agent after lenvatinib, according to the results of the present study. Regorafenib has the potential to become an appropriate posttreatment agent after lenvatinib.

Comparison of systemic therapy efficacy in advanced hepatocellular carcinoma: Systematic review and frequentist network meta-analysis of randomized controlled trials.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 293-293
Author(s):  
Robin Park ◽  
Laércio Lopes da Silva ◽  
Voravech Nissaisorakarn ◽  
Ivy Riano ◽  
Anwaar Saeed
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Meta Analysis ◽  
Objective Response ◽  
Indirect Comparison ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
First Line ◽  
Line Setting ◽  
Systemic Agents

293 Background: Several systemic agents are approved for use in the first line and second line treatment settings for advanced hepatocellular carcinoma (aHCC). However, choosing among available options in both first and second line settings remain difficult due to the paucity of head-to-head comparative trials. Therefore, we have conducted a systematic review and network meta-analysis for the indirect comparison of the systemic agents in the first line and second line settings. Methods: Published clinical trials that have evaluated systemic agents in the first line and second line settings in advanced HCC from inception to April 2020 were identified by searching PubMed, EMBASE, and Cochrane Databases and abstracts presented in the main annual ASCO and ESMO conferences from 2017 to 2020. Studies published in English providing clinical outcomes data including overall survival (OS), progression free survival (PFS) and objective response rate (ORR) were included in the analysis. The primary outcomes of interest were pooled hazard ratios (HR) of OS and OR of ORR in first line studies and HR of PFS and OR of ORR for second line studies. OS for second line agents were synthesized in a qualitative analysis. Results: Overall, 8,335 patients (13 studies) and 4,612 patients (11 studies) were analyzed in phase II/III trials for first line and second line settings respectively. In the first line setting, atezolizumab plus bevacizumab and lenvatinib were ranked highest as the regimens associated with the greatest OS (A+B, HR 0.58, 95% CI, 0.42-0.80; P-score 0.993) and ORR (lenva, OR 3.34, 95% CI, 2.17-5.14; P-score 0.080) respectively. In the second line setting, cabozantinib showed the highest probability of greatest PFS benefit (HR 0.44, 95% CI, 0.29-0.66; P-score 0.854) as well as the highest probability of greatest ORR benefit (cabo, OR 9.40, 95% CI, 1.25-70.83, P-score, 0.266). Conclusions: In the first line setting, atezolizumab plus bevacizumab may be the superior regimen whereas lenvatinib may be considered as the initial option when robust tumor responses are preferred. In the second line setting, cabozantinib may be the preferred option including in cases when robust tumor responses are favored.

scholarly journals The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 343
Author(s):  
Jing-Houng Wang ◽  
Yen-Yang Chen ◽  
Kwong-Ming Kee ◽  
Chih-Chi Wang ◽  
Ming-Chao Tsai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Neutrophil To Lymphocyte Ratio ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Lymphocyte Ratio ◽  
Third Line

Atezolizumab plus bevacizumab has been approved as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma (uHCC). This study was designed to assess the clinical impact of atezolizumab plus bevacizumab in uHCC patients. A total of 48 uHCC patients receiving atezolizumab plus bevacizumab were identified, including first-line, second-line, third-line, and later-line settings. In these patients, the median progression-free survival (PFS) was 5.0 months, including 5.0 months for the first-line treatment, not reached for the second-line treatment, and 2.5 months for the third line and later line treatment. The objective response rate and disease control rate to atezolizumab plus bevacizumab were 27.1% and 68.8%, respectively. The severity of most adverse events was predominantly grade 1–2, and most patients tolerated the toxicities. The ratios of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) were used to predict PFS in these patients. The optimal cutoff values of NLR and PLR were 3 and 230, and NLR and PLR were independent prognostic factors for superior PFS in the univariate and multivariate analyses. Our study confirms the efficacy and safety of atezolizumab plus bevacizumab in uHCC patients in clinical practice and demonstrates the prognostic role of NLR and PLR for PFS in these patients.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

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.

Update on overall survival (OS) of RESCUE: An open-label, phase 2 trial of camrelizumab (C) in combination with apatinib (A) in patients with advanced hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4076-4076
Author(s):  
Yun Zhang ◽  
Jianming Xu ◽  
Jie Shen ◽  
Shanzhi Gu ◽  
Lihua Wu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Durable Response ◽  
Advanced Hcc ◽  
Phase 2 Trial ◽  
Open Label Phase

4076 Background: C+A combination therapy displayed high objective response rate, disease control rate, and durable response with a manageable safety profile in patients (pts) with advanced HCC. Here we performed an updated analysis of OS to characterize the OS benefit of C+A in HCC pts. Methods: 70 pts in first-line cohort and 120 pts in second-line cohort were enrolled. Median OS and 2-year OS rate were evaluated via updated data (data cutoff, 3 January, 2021). Median time from enrollment to data cutoff of the total population (N = 190) was 29.1 months (range, 24.0-33.7). Results: OS events had occurred in 58.6% pts in first-line cohort and 60.0% pts in second-line cohort. The median OS was 20.1 months (95% CI, 14.9-NR) and 2-year OS rate was 43.3% (95% CI, 31.3-54.7) in first-line cohort. The median OS was 21.8 months (95% CI, 17.3-26.8) and 2-year OS rate was 44.6% (95% CI, 35.5-53.3) in second-line cohort. Conclusions: Long-term follow-up of C+A demonstrated remarkable survival benefit in advanced HCC pts, which further suggested that C+A is a promising combination therapy in advanced HCC pts. Clinical trial information: NCT03463876.

Late Onset Neutropenia like a Complication of Treatment with Anti-CD20.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4701-4701
Author(s):  
Araceli Rubio-Martinez ◽  
Valle Recasens ◽  
Ana Godoy ◽  
Noelia Padron ◽  
Pilar Giraldo
Keyword(s):  
Combination Therapy ◽  
Cox Regression ◽  
Late Onset ◽  
Demographic Data ◽  
Second Line ◽  
First Line ◽  
Who Grade ◽  
Severe Infections ◽  
Third Line ◽  
Anti Cd20

Abstract Introduction: The occurrence of unexplained peripheral blood cytopenia, particularly neutropenia, has been recently reported after rituximab ®. Its prevalence may be underestimated since it may occur late after treatment (Cattaneo C et al Leuk Lymphoma. 2006 Jun;47(6):965–6, Chaiwatanatorn K et al Br J Haematol 2003). Apparently the risk is higher when R is associated with Fludarabine in combination therapy, producing a decrease in bone marrow precursors. Patients and methods: observational and retrospective study in order to determine the incidence of WHO grade III – IV neutropenia (neutrophils: ≤ 0.6×109/L) and the development of infection complications in patients treated with R-CMF or R-CF in our hospital from 6/8/2003 to 20/3/2006. We have compared these data with the incidence of delayed neutropenia during 621 courses of R or R-CHOP administered as outpatient schedule in the same period. Data source: clinical reports. Variables: demographic data (age, gender), date of diagnosis, histological type, schedule therapy, number of cycles, clinical response (complete remission (CR), partial remission (PR), and non response (NR), prophylaxis with G-CSF, blood counts (leucocytes, neutrophils, hemoglobin and platelets) during all treatment and follow-up, infections and number of admissions in the hospital. Kaplan-Meier survival and Cox regression were calculated. Results: From 78 courses of Immuno-chemotherapy in 16 consecutive patients diagnosed of follicular NHL: 10, B-CLL: 5, mantle NHL: 1. R-CMF (14 patients), R-CF (2 patients). (9 males/7 females), mean age 58.75 (20–78). In first line 8, second line 6 and third line 2. Number of courses received: mean 4,8 (1–6). Response: CR:13, NR: 1, Non valuable: 2. G-CSF prophylaxis during therapy in 50%. 9 patients (56.2%) developed neutropenia during the treatment or in the following year, one of them had also anemia and thrombocytopenia. In 4 patients the combination therapy was administered in first line, 3 as second line and 2 as third line therapy. Patients received 5 (6 courses), 1 (5 courses), 1 (3 courses), 1 (2 courses) and 1 (1 course), 8 developed infections that required admission into hospital (1 died after third course by sepsis). Another two patients developed severe infections without neutropenia. A late and persistent neutropenia after to finish therapy (1–6 months later), was observed in 4 patients (duration:3, 12, 11 and 4 months); 2 patients got over at 11 and 12 months after and in two of them is present now. They were treated with G-CSF, prednisone and cyclosporine in 2 cases without response and reached normal values when we associated IV immunoglobulins extract. OS: mean 26.4 months (6–49), RFS: 10.6 months (1–30). Conclusions: Delayed-onset cytopenia, particularly neutropenia, is a clinically significant complication of rituximab treatment when it is administered in combination with Fludarabine increasing the risk of severe infections.

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