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

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.

Download Full-text

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

Liver Cancer ◽

10.1159/000507022 ◽

2020 ◽

Vol 9 (4) ◽

pp. 382-396 ◽

Cited By ~ 3

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.

Download Full-text

Unresectable hepatocellular carcinoma: prospects for drug therapy with lenvatinib

Malignant tumours ◽

10.18027/2224-5057-2021-11-3-45-52 ◽

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.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.560 ◽

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.

Download Full-text

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

Journal of Medical Sciences ◽

10.4103/jmedsci.jmedsci_156_17 ◽

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

Download Full-text

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 ◽

10.3390/cancers12102906 ◽

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.

Download Full-text

A phase I/II trial to evaluate cabozantinib in patients with advanced hepatocellular carcinoma with Child-Pugh class B cirrhosis after first-line therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.tps357 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. TPS357-TPS357

Author(s):

Thomas Enzler ◽

Neehar Parikh ◽

Chih-Yi Liao ◽

Aparna Kalyan ◽

David Hsieh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase I ◽

Systemic Treatment ◽

Advanced Hepatocellular Carcinoma ◽

First Line ◽

Early Stage Disease ◽

Advanced Hcc ◽

Line Therapy ◽

Class B ◽

Pugh Class

TPS357 Background: Hepatocellular carcinoma (HCC) is the 4th leading cause of cancer related death worldwide. HCC typically develops in patients with cirrhosis and has a 5-year survival estimate of 20%. Only patients with early stage disease may be eligible for a curative approach using local treatment and/or transplant. The majority of patient present with advanced HCC and will require systemic treatment for disease control. Several systemic therapies are FDA-approved for the treatment of HCC; however, they are only approved for patients with Child-Pugh class A cirrhosis. There are limited data and no approved second-line therapy for HCC with more advanced cirrhosis, including Child-Pugh class B, which represents a significant proportion of patients. The aim of this trial is to determine the safety and efficacy of cabozantinib, a multi-kinase inhibitor, in patients with HCC with Child-Pugh class B cirrhosis. Methods: This investigator-initiated, phase I/II study is enrolling 32 patients with advanced HCC, Child-Pugh B7 or B8, who have previously received first-line systemic treatment. Patients receive cabozantinib at one of 3 dose levels (20 mg, 40 mg, and 60 mg) with a starting dose level of 40 mg to evaluate the safety profile and obtain the recommended phase 2 dose (RP2D). The primary endpoint is assessment of dose-limiting toxicity with a null hypothesis greater than 35%. Secondary endpoints include ORR per RECIST v1.1, PFS, OS, and PK profile. Exploratory endpoints include whole exome/RNAseq analysis (including MET, VEGF, AXL, and immune signature), spatial profiling of immune markers by multiplex immunofluorescence, and specimen banking (tissue, blood and imaging). The trial design is based on the Time-To-Event modification of the Continual Reassessment Method (TiTE-CRM), which allows for continued monitoring of toxicity as a function of a dose-over-time, and is flexible with regard to the number of patients treated at a certain dose. The trial is open at University of Michigan as lead and coordinating site, and due to open at 3 additional high-volume centers. Clinical trial information: 04497038.

Download Full-text