Unresectable hepatocellular carcinoma: prospects for drug therapy with lenvatinib

2022 ◽  
Vol 11 (3) ◽  
pp. 45-52
Author(s):  
V.  V. Breder ◽  
D.  T. Abdurakhmanov ◽  
V.  V. Petkau ◽  
P.  V. Balakhnin ◽  
M.  V. Volkonsky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Therapy ◽  
Liver Function ◽  
Real World ◽  
Systemic Therapy ◽  
Efficacy And Safety ◽  
Study Results ◽  
Class B ◽  
Pugh Class ◽  
Positive Results

There is a number of unresolved issues regarding the systemic therapy administration for hepatocellular carcinoma (HCC). Their solution is facilitated by accumulating real‑world study results. Lenvatinib therapy is a recognized drug with a good efficacy and safety profile for the treatment of HCC. Subanalyses of the REFLECT study showed that the absence of stratification by baseline AFP and baseline liver function, as well as the lack of options for subsequent drug therapy after lenvatinib, also affects the outcomes. Once these factors are taken into account, the hypothesis of superiority of lenvatinib to sorafenib and other drugs can be tested. Real‑world clinical studies have demonstrated positive results of lenvatinib therapy in patients with Child‑Pugh class B liver function, provided recommendations on the sequence of systemic therapy after lenvatinib and on the use of lenvatinib in patients with BCLC stage B, along with considering the possibility of lenvatinib monotherapy and the prospects for its use in patients with nHCC. Further real‑world studies of lenvatinib for HCC in the Russian population are required.

scholarly journals Complete response to the combination of Lenvatinib and Pembrolizumab in an advanced hepatocellular carcinoma patient: a case report

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhaonan Liu ◽  
Xingjie Li ◽  
Xuequn He ◽  
Yingchun Xu ◽  
Xi Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Arterial Embolization ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Class B ◽  
Embolization Treatment ◽  
History Of ◽  
Pugh Class ◽  
Patient’S History

Abstract Background The majority of patients diagnosed with hepatocellular carcinoma (HCC) have advanced diseases and many are not eligible for curative therapies. Case presentation We report a rare case of HCC from a patient who had a complete response (CR) with the use of combination of Lenvatinib and Pembrolizumab. A 63-year-old man presented at the hospital with serious abdominal pain and was found to have a mass with heterogeneous enhancement and with hemorrhage in segment III of the liver after the examination of abdominal computerized tomography (CT) scan. The patient’s history of viral hepatitis B infection, liver cirrhosis and the ɑ-fetoprotein (AFP) level of 14,429.3 ng/ml supported the clinical diagnosis of HCC and laboratory results demonstrated liver function damage status (Child-Pugh class B, Score 8). The patient first received hepatic arterial embolization treatment on 28th November 2017. At this stage supportive care was recommended for poor liver function. In February 2018, combined immunotherapy of Pembrolizumab (2 mg/kg, q3w) and Lenvatinib (8 mg–4 mg, qd) were performed. Nine months following the treatment he had a CR and now, 22 months since the initial treatment, there is no clinical evidence of disease progression. The current overall survival is 22 months. Conclusions HCC is a potentially lethal malignant tumor and the combination of immunotherapy plus anti-angiogenic inhibitors shows promising outcome for advanced diseases.

Clinical outcomes of hepatocellular carcinoma patients with Child-Pugh class B treated with stereotactic body radiation therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 560-560
Author(s):  
J Richelcyn Baclay ◽  
Diego Augusto Santos Toesca ◽  
Rie von Eyben ◽  
Madeline Minneci ◽  
Erqi L. Pollom ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Clinical Laboratory ◽  
Score Change ◽  
Related Data ◽  
Institutional Review Board Approval ◽  
Institutional Review ◽  
Class B ◽  
Pugh Class

560 Background: Caution is usually employed in the treatment of patients with hepatocellular carcinoma (HCC) due to the inherent liver radiosensitivity, especially in patients with Child Pugh (CP) B and C classes. This study aims to review the outcomes of patients treated with SBRT for CP class B with HCC. Methods: Medical records of all patients with HCC and compromised liver function (CP class B) treated with SBRT between 2003 and 2018 were retrieved after institutional review board approval. Clinical, laboratory, and treatment-related data were collected and analyzed for their correlation to toxicity and survival. Liver function was assessed prior to SBRT and at 1, 3 and 6 months after treatment using the CP score classification. Patients were censored for toxicity after extensive tumor progression in the liver, new liver-directed therapies, or liver transplant. Time-to-events were calculated from date of SBRT. Results: A total of 22 patients were identified, but 3 were excluded for incomplete follow-up. Median follow-up time was 33 months (range: 11-95 months). At baseline, 13 (68%) patients had a CP score of 7, and 6 (32%) had a CP score of 8. The median PTV volume was 94 cc (range: 14-710 cc). The median prescribed dose was in 5 fractions (range: 35-45 Gy in 3-5 fractions). After SBRT, 8 (42%) patients presented with worsening in CP score, with a mean increase of 1.5 points (95% CI, 0.6-2.5; p = 0.005) at the first month of follow-up, but followed by recovery in liver function with change in CP score not statistically different from baseline at 3- or 6-month follow-up times (p = 0.35 and p = 0.13, respectively). Eight patients (42%) presented with acute hepatobiliary toxicity, with six of those presenting with ≥grade 2 toxicity. Patients with CP score change ≥2 points (n = 6) showed a significantly higher incidence of acute grade 2 or higher hepatobiliary toxicity (p = 0.001) with a trend toward worse overall survival (33 vs. 51 months, p = 0.45). Conclusions: In our cohort, SBRT demonstrated to be safe for patients with Child Pugh Class B liver function.

Application of stereotactic ablative radiotherapy in hepatocellular carcinoma patients with child–Turcotte–Pugh Class B liver function

2020 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
Chun-Shu Lin ◽  
Cheng-Hsiang Lo ◽  
Wen-Yen Huang ◽  
Wei-Chou Chang ◽  
Hsing-Lung Chao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Stereotactic Ablative Radiotherapy ◽  
Class B ◽  
Pugh Class

scholarly journals Liver Function Changes in Patients with Hepatocellular Carcinoma Treated with Lenvatinib: Predictive Factors of Progression to Child-Pugh Class B, the Formation of Ascites and the Candidates for the Post-Progression Treatment

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2906
Author(s):  
Takeshi Hatanaka ◽  
Satoru Kakizaki ◽  
Tamon Nagashima ◽  
Masashi Namikawa ◽  
Takashi Ueno ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analysis ◽  
Platelet Count ◽  
Liver Function ◽  
Predictive Factors ◽  
Intermediate Stage ◽  
Class B ◽  
Low Platelet Count ◽  
Pugh Class ◽  
Careful Screening

The aim of this multicenter retrospective study was to assess the change in liver function in patients with hepatocellular carcinoma treated with lenvatinib. Among 139 consecutive patients receiving lenvatinib treatment between March 2018 and July 2019, 28 patients with Child-Pugh class B and one patient with inadequate patient information were excluded. Remaining 110 patients with Child-Pugh class A were analyzed. The median age of 110 patients was 73 years (IQR 66.7–80) and 88 patients (80.0%) were men. Child-Pugh score was 5 (CP5A) and 6 (CP6A) in 58 (52.7%) and 52 patients (47.3%), and ALBI grade was 1 and 2 in 38 (34.5%) and 72 patients (65.5%), respectively. The deterioration to Child-Pugh class B was found in 43 patients (39.1%) during the lenvatinib treatment. The favorable factors related to preserving liver function were significantly shown to be male, ALBI grade 1, CP5A and BCLC early or intermediate stage in the multivariate analysis. The formation of ascites was found in 32 patients (28.6%). The significant unfavorable factors associated with the formation of ascites were found to be low platelet count and CP6A. Among the 79 patients, there were 36 (45.6%) and 11 patients (13.9%) who fulfilled the criteria for candidate for the post-progression treatment and ramucirumab treatment, respectively. The predictive factors of the post-progression treatment were shown to be ALBI grade 1 and CP5A in multivariate analysis. In conclusion, male, ALBI grade 1, CP5A and BCLC early or intermediate stage were favorable factors related to sustaining liver function and the patients with ALBI grade 1 and CP5A were eligible for the post-progression treatment. Careful screening for ascites was needed in patients with low platelet count and CP6A.

scholarly journals Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 382-396 ◽  
Author(s):  
Susumu Maruta ◽  
Sadahisa Ogasawara ◽  
Yoshihiko Ooka ◽  
Masamichi Obu ◽  
Masanori Inoue ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Objective Response ◽  
Dose Intensity ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
High Burden ◽  
Advanced Hcc ◽  
Class B ◽  
Pugh Class

Background: The present study aimed to assess the efficacy and safety of lenvatinib and verify the possibility of lenvatinib for the expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma (HCC) in real-world practice, primarily focusing on the population that was excluded in the REFLECT trial. Methods: We retrospectively collected data on patients with advanced HCC who were administered lenvatinib in 7 institutions in Japan. Results: Of 152 advanced HCC patients, 95 and 57 patients received lenvatinib in first-line and second- or later-line systemic therapies, respectively. The median progression-free survival in Child-Pugh class A patients was nearly equal between first- and second- or later-line therapies (5.2 months; 95% CI 3.7–6.9 for first line, 4.8 months; 95% CI 3.8–5.9 for second or later line, p = 0.933). According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate of 27 patients (18%) who showed a high burden of intrahepatic lesions (i.e., main portal vein and/or bile duct invasion or 50% or higher liver occupation) at baseline radiological assessment was 41% and similar with that of other population. The present study included 20 patients (13%) with Child-Pugh class B. These patients observed high frequency rates of liver function-related adverse events due to lenvatinib. The 8-week dose intensity of lenvatinib had a strong correlation with liver function according to both the Child-Pugh and albumin – bilirubin scores. Conclusion: Lenvatinib had potential benefits for patients with advanced HCC with second- or later-line therapies and a high burden of intrahepatic lesions. Dose modification should be paid increased attention among patients with poor liver function, such as Child-Pugh class B patients.

scholarly journals Effectiveness and Safety of Nivolumab in Child–Pugh B Patients with Hepatocellular Carcinoma: A Real-World Cohort Study

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1968 ◽  
Author(s):  
Won-Mook Choi ◽  
Danbi Lee ◽  
Ju Hyun Shim ◽  
Kang Mo Kim ◽  
Young-Suk Lim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Real World ◽  
Objective Response ◽  
Real World Data ◽  
Durable Response ◽  
Class B ◽  
Pugh Class ◽  
Unselected Child ◽  
Negative Predictor

Nivolumab has shown durable response and safety in patients with hepatocellular carcinoma (HCC) in previous trials. However, real-world data of nivolumab in HCC patients, especially those with Child–Pugh class B, are limited. To investigate the effectiveness and safety of nivolumab in a real-world cohort of patients with advanced HCC, we retrospectively evaluated 203 patients with HCC who were treated with nivolumab between July 2017 and February 2019. Of 203 patients, 132 patients were classified as Child–Pugh class A and 71 patients were Child–Pugh class B. Objective response rate was lower in patients with Child–Pugh class B than A (2.8% vs. 15.9%; p = 0.010). Child–Pugh class B was an independent negative predictor for objective response. Median overall survival was shorter in Child–Pugh B patients (11.3 vs. 42.9 weeks; adjusted hazard ratio [AHR], 2.10; p < 0.001). In Child–Pugh B patients, overall survival of patients with Child–Pugh score of 8 or 9 was worse than patients with Child–Pugh score of 7 (7.4 vs. 15.3 weeks; AHR, 1.93; p < 0.020). In conclusion, considering the unsatisfactory response in Child–Pugh B patients, nivolumab may not be used in unselected Child–Pugh B patients. Further studies are needed in this patient population.

scholarly journals Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Liver Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Myung Ji Goh ◽  
Joo Hyun Oh ◽  
Yewan Park ◽  
Jihye Kim ◽  
Wonseok Kang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Disease Progression ◽  
Real World ◽  
Medical Center ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Background:</i></b> Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. <b><i>Methods:</i></b> A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. <b><i>Results:</i></b> A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. <b><i>Conclusion:</i></b> Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

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]

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