scholarly journals Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Liver Cancer ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Yeonghak Bang ◽  
Neung Hwa Park ◽  
Jung Woo Shin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Analysis ◽  
Real World ◽  
Checkpoint Inhibitors ◽  
Clinical Trial Data ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
First Line

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.

Real-world efficacy and safety of lenvatinib-base therapy for patients with unresectable hepatocellular carcinoma in China: A multicenter retrospective analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16192-e16192
Author(s):  
Qicong Mai ◽  
Song Chen ◽  
Feng Shi ◽  
Zhiqiang Mo ◽  
Jian He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Grade 3

e16192 Background: Lenvatinib has been approved as a first-line systemic for advanced hepatocellular carcinoma (HCC) after the randomized phase III REFLECT trial. The aim of this study was to assess the lenvatinib-base treatment patterns and safety in real-world clinical settings in China. Methods: In this multicenter retrospective study, A total of 278 patients with unresectable HCC were treated with lenvatinib-base treatment between October 2018 and November 2020 were analyzed. Therapeutic effect was determined using the RECIST 1.1 and mRECIST criteria. Progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAE) were also evaluated. Results: Of 278 unresectable HCC patients (median age: 56.1±11.9 years), 220 (79.1%) had cirrhosis caused by HBV infection. 215 (77.3%) and 63 (22.7%) patients were classified as Child-pugh A and B class, respectively. 233 (83.8%) and 45 (16.2%) patients received lenvatinib in first-line and second-line systemic therapies, respectively. 223 (80.2%) patients were treated with lenvatinib plus arterially directed therapy (TACE or HAIC of FOLFOX) and 55 (19.8%) were treated with lenvatinib alone. The objective response rate were 34.9% (RECIST) and 47.5% (mRECIST), while the disease control rate were 75.5%. With a median follow-up period of 12.8 months, the median PFS and OS were 7.8 months (95% CI 7.1–8.4) and 17.2 months (95% CI 14.9–19.6), respectively. Results from the multivariate analysis showed that the significant independent favorable prognosis factors were tumor burden< 50% (P=0.033), Child–Pugh A class (P<0.01), AFP level <200ng/mL (P=0.045), the combination with lenvatinib and arterially directed therapy (P<0.01). TRAE occurred in 219 of 278 patients (78.8%), most common TRAE were hypertension (n=118; 42.4%) and hand-foot skin reaction (n=91; 32.7%). The most common grade 3–4 TARE were hypertension (n=23; 8.3%), decreased appetite (n=18; 6.5%), AST elevation (n=14; 5%), and diarrhea (n=14; 5%) across all study patients. Conclusions: In this multicenter real-world study, lenvatinib-base treatment could be accomplished with well tolerated and response for unresectable HCC patients. Combination with arterially directed therapy could likely improve the overall survival.

Efficacy and safety of lenvatinib in the real-world treatment of hepatocellular carcinoma: Results from a Canadian multicenter database (HCC CHORD).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 275-275
Author(s):  
Carla Pires Amaro ◽  
Michael J Allen ◽  
Jennifer J. Knox ◽  
Erica S Tsang ◽  
Howard John Lim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
The Real ◽  
First Line Therapy

275 Background: The REFLECT trial establishedlenvatinib (LEN) as a first-line treatment option for hepatocellular carcinoma (HCC). Compared to sorafenib (S), LEN has a higher objective response rate (ORR) and progression-free survival (PFS) with a slightly different toxicity profile. The aim of this study was to gather data regarding the efficacy and safety of LEN when used in the real-world treatment of HCC. To our knowledge, this is the first study to examine LEN use in HCC patients treated outside of Asia. Methods: HCC patients treated with LEN from 10 cancer centers in the Canadian provinces of British Columbia, Alberta, Ontario and Nova Scotia between July 2018 to July 2020 were included. Overall survival (OS), PFS, disease control rate (DCR) and ORR were retrospectively analyzed and compared across first- and second-to-fourth line use of LEN. ORR was determined radiographically according to the treating physician´s opinion in clinical notes and not RECIST 1.1 or mRECIST. Toxicities were also examined. Results: A total of 220 patients were included in this analysis. Median age was 67 years, 80% were men and 25.5% East Asian. The most frequent causes of liver disease were hepatitis C (37%) and B (26%). 62% of patients received any localized treatment before LEN, of those 26% had TACE, 15% TARE and 7.7% had liver transplant. Before starting LEN 29% of patients were ECOG 0 and 59% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (75.5%). Main portal vein invasion was present in 14% of the patients. Median follow-up was 4.5 months. A total of 173 patients (79%) received LEN as first line therapy and 47 patients (21%) were treated in second-to-fourth line. Of patients receiving LEN in first line, 22 (13%) started treatment with S, but switched to LEN before progression due to poor tolerance of S. ORR, DCR, PFS and OS are shown in the table. Toxicities occurred in 86% of patients and led to dose reductions in 76 (35%) patients and drug discontinuation in 53 (24%) patients. The most common side effects were fatigue (59%), hypertension (41%), decreased appetite (25%) and diarrhea (22%). Conclusions: Outcomes of HCC patients treated in Canada with LEN in the first line are comparable to those demonstrated in the REFLECT trial, despite the inclusion of Child-Pugh B and ECOG >1 patients. LEN use in second or later lines also showed similar outcomes, although more conclusions are difficult to draw due to the small numbers. LEN appears to be effective and safe in real world practice outside of Asia in first- and second-to-fourth line treatment of HCC. [Table: see text]

The Role of the Albumin-Bilirubin Score for Predicting the Outcomes in Japanese Patients with Advanced Hepatocellular Carcinoma Treated with Ramucirumab: A Real-World Study

Oncology ◽  
2020 ◽  
pp. 1-12
Author(s):  
Takeshi Hatanaka ◽  
Atsushi Naganuma ◽  
Mitsuhiko Shibasaki ◽  
Tatsuya Kohga ◽  
Yosuke Arai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real World ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Low Incidence ◽  
Number Of Cycles

<b><i>Aim:</i></b> The aim of this retrospective study was to investigate the efficacy and safety of ramucirumab treatment under real-world conditions and to clarify the role of albumin-bilirubin (ALBI) score in predicting outcomes. <b><i>Methods:</i></b> Between June 2019 and May 2020, a total of 16 patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab in Gunma Saiseikai Maebashi Hospital and its affiliated hospitals was included. <b><i>Results:</i></b> The median age was 71 (interquartile range [IQR] 65–74) years old, and 12 patients (75.0%) were male. The modified ALBI (mALBI) grade was 1, 2a, and 2b at baseline in 4 (25.0%), 3 (18.8%), and 9 patients (56.3%), respectively. The Barcelona Clinic Liver Cancer stage was intermediate and advanced stage in 1 (6.3%) and 15 patients (93.8%), respectively. The serum α-fetoprotein at baseline was 4,911 (IQR 2,091–17,377) ng/mL. The disease control rate in patients with mALBI grade1 + 2a was significantly higher than in those with mALBI grade 2b (100 vs. 28.6%, <i>p</i> = 0.028). The patients with mALBI grade 1 + 2a had a significantly better overall survival (OS) and longer progression-free survival (PFS) than those with mALBI grade 2b (median OS 6.7 vs. 3.0 months; <i>p</i> = 0.036, median PFS 7.5 vs. 1.4 months; <i>p</i> = 0.002). The number of cycles of ramucirumab treatment was significantly correlated with the ALBI score (<i>r</i> = −0.452, <i>p</i> = 0.030). The patients with mALBI grade 1 + 2a showed a low incidence of adverse events (AEs) and discontinuation due to AEs. <b><i>Conclusions:</i></b> Advanced HCC patients with mALBI grade 1 + 2a may be a good indication for ramucirumab treatment.

The cost-effectiveness of new first-line therapies approved in advanced hepatocellular carcinoma

2021 ◽  
pp. 107815522110450
Author(s):  
Jacopo Giuliani ◽  
Beatrice Mantoan ◽  
Andrea Bonetti
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cost Effectiveness ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Control Groups ◽  
First Line ◽  
Free Survival ◽  
The Difference ◽  
The Cost

The introduction of targeted agents (lenvatinib) and immune-based therapies (atezolizumab in combination with bevacizumab) for first-line advanced hepatocellular carcinoma provided new therapeutic options. The aim of this paper was to assess the cost-effectiveness of lenvatinib and the combination of atezolizumab plus bevacizumab in first-line for advanced hepatocellular carcinoma. Pivotal phase III randomized controlled trials were considered. Incremental cost-effectiveness ratio was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression free survival). One thousand four hundred and fifty five patients were included. The lowest cost for month of progression free survival-gain was associated with lenvatinib, with 139.24 € per month progression free survival-gained. Combining pharmacological costs of drugs with the measure of efficacy represented by progression free survival, lenvatinib is a cost-effective treatment in first-line for advanced hepatocellular carcinoma.

An exploratory study of sorafenib plus toripalimab for unresectable hepatocellular carcinoma with portal vein tumor thrombus.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4658-TPS4658
Author(s):  
Yu Yang ◽  
Qiu Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Monoclonal Antibody ◽  
Portal Vein ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

TPS4658 Background: Portal vein tumor thrombosis (PVTT) is common among advanced hepatocellular carcinoma ( HCC), resulting in poor prognosis. As the standard first-line treatment, the efficacy of Sorafenib is not satisfactory in HCC with PVTT. Although immune checkpoint inhibitors have made a breakthrough in treatment of advanced HCC, objective response rate (ORR) of anti-PD-1 monoclonal antibody monotherapy is only 17-20%. Recently, PD-1/PD-L1 inhibitors combined with anti-angiogenesis therapy have shown good efficacy in the clinical studies. However, the data on immunotherapy for HCC with PVTT are still limited. Toripalimab is the first Chinese-produced anti-PD-1 monoclonal antibody marketed. We designed the study to evaluate the efficacy and safety of Sorafenib plus Toripalimab as the first-line treatment for unresectable HCC with PVTT. Methods: The study is a multicenter, single-arm, phase Ib/II trial. The primary objectives are 6-month progression-free survival (PFS) rate and safety. Secondary objectives include ORR, disease control rate, PFS, overall survival. The escalation stage includes two dose cohorts: Sorafenib 400 mg po qd or 400 mg bid combined with Toripalimab 240 mg iv d1 q3w. 6-12 patients are estimated to evaluate the dose-limiting toxicity within the first 42 days of administration. In the expansion stage, patients are treated with the recommended dose based on the escalation stage, until progressive disease or intolerable toxicity. Assuming Sorafenib plus Toripalimab can improve the 6-month PFS rate to 40% (Sorafenib:20%, β = 0.2, α = 0.05) and dropout is 10%, this stage need 39 patients. A total of 45-51 patients are enrolled. Major eligibility requirements include: unresectable HCC with diagnoses confirmed histologically or cytologically, or confirmed clinically in accordance with Chinese guideline for HCC diagnosis and treatment (v2017); radiographic evidence of PVTT; age ≥18 and < 75 years; at least one measurable lesion according to RECIST 1.1; a predicted life expectancy ≥ 3 months; ECOG PS≤1, Child-Pugh class A or B (≤7); no any prior systemic anti-cancer treatment; adequate organ function. Patients with hepatitis B treated with antiviral therapy (viral load < 100 IU/mL) or patients with chronic hepatitis C can be included. The study is open and actively enrolling at time of submission. Clinical trial information: NCT04069949 .

Efficacy and safety of lenvatinib (LEN) in Korean patients (pts) with advanced hepatocellular carcinoma (aHCC): Multicenter retrospective analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 490-490
Author(s):  
Jaekyung Cheon ◽  
Changhoon Yoo ◽  
Yeonghak Bang ◽  
Hong Jae Chon ◽  
Baek-Yeol Ryoo
Keyword(s):  
Retrospective Analysis ◽  
Checkpoint Inhibitors ◽  
Real Life ◽  
Daily Practice ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
First Line ◽  
Disease Extent ◽  
Line Setting

490 Background: LEN has demonstrated the efficacy and safety in pts with aHCC as first-line treatment in the pivotal REFLECT trial. Further evaluation in real-world setting is necessary to measure the clinical outcomes of LEN in daily practice. Methods: This is a multicenter retrospective analysis from 3 Korean referral cancer institutions. Between September 2018 and August 2019, a total of 74 pts received LEN for the management of BCLC B or C aHCC, and 66 pts who had at least one follow-up visit after the start of LEN were included in this analysis. Results: Median age was 58 years (range, 19-81), and 46 pts (69.7%) were male. Baseline characteristics were as follows; Child-Pugh class A/B/C in 46 (69.7%)/14 (21.2%)/6 (9.1%), BCLC B/C/D in 1 (1.5%)/63 (95.5%)/2 (3.0%), prior systemic therapy in 25 (37.9%) including 14 (21.2%) with prior immune checkpoint inhibitors (ICIs). LEN was used as first/second/third to fourth lines of therapy in 41 (62.1%)/13 (19.7%)/12 (18.2%) pts, and 27 (40.9%) had extensive disease extent excluded in the REFLECT trial. With a median follow-up duration of 4.8 months (95% CI, 3.4–6.1), the median PFS and OS were 4.6 (95% CI, 3.2-6.0) and 7.5 months (mo) (95% CI, 3.7–11.2), respectively, in overall pts: first-line setting, 4.2 (95% CI, 3.2-5.2) and 6.5 mo (95% CI, 5.0-8.1), respectively; ≥ second-line setting, 6.1 mo (95% CI, 3.6–8.5) and not reached, respectively. In pts with prior ICIs, median PFS was 6.1 mo (95% CI, 1.8-8.4) and median OS was not reached. According to the RECIST v 1.1, response rates and disease control rate were 12.1% and 71.2%, respectively, in overall pts. The most common grade 3-4 toxicities were hyperbilirubinemia (n=9, 13.6%), AST elevation (n=5, 7.6%), diarrhea (n=4, 6.1%) and fatigue (n=4, 6.1%). Conclusions: LEN was effective and well tolerated in pts with aHCC in Korean real-life setting.

Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian center.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 559-559
Author(s):  
Kennedy Ng ◽  
Lawrence Wen Jun Wong ◽  
Su Pin Choo ◽  
David Wai-Meng Tai ◽  
Sze Huey Tan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Adverse Events ◽  
Real World ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Advanced Hcc ◽  
Increased Risk

559 Background: Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety however is lacking, more so when used in patients who fall out of standard clinical trial criteria. Methods: We conducted a retrospective review of all patients with advanced HCC seen at our centre who received at least one dose of an ICI between May 2015 - June 2018. Data cutoff was 31 Dec 2018. Responses were evaluated using RECIST v1.1 criteria. Results: 114 patients fulfilled inclusion criteria. Median age was 66 years and 88.6% were male. 96.5% had an ECOG PS of 0 – 1. 64.9% received an ICI within a clinical trial setting. 62.3% received monotherapy ICI. 19.6% of patients had Child-Pugh B disease on initiation of ICI, and 69.3% had an ALBI Grade of 2. 50.0% were known to have hepatitis B and 11.4% had hepatitis C. Baseline HBV VL ranged from undetectable to 8210000 IU/mL. 30.7% received prior systemic treatment, most commonly sorafenib (82.9%). Over a median follow-up duration of 5.7 months (0.03 - 42.4), ORR was 18.4%, and disease control rate (DCR) was 51.8%. Median PFS was 2.6 months (1.7 - 3.9), and median OS was 13.9 months (7.0 - 16.2). 5 patients (23.8%) had response duration of more than 18 months. 35.1% received further systemic therapy after ICI. On multivariable analyses, age ≥ 65 years, higher albumin level and lower bilirubin level were associated with increased OS. 68.0% of patients experienced adverse events (AEs) of any grade, 12.0% of these being grade 3 - 4. No grade 5 adverse events were observed. Use of antiviral therapy was associated with a lower risk of hepatic AEs (p = 0.04) whilst high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AEs. Conclusions: In the real-world setting, responses and adverse event profiles to ICI use are comparable to those observed in clinical trials despite a more heterogenous population base. The expansion of indications for ICI use in advanced HCC beyond current approvals warrants greater study.

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