Adjuvant Lenvatinib Prevents Recurrence of High-risk Patients With HBV-related HCC After Liver Transplantation
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Recurrence
Study type: Observational

Summary: 
      High-risk patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) suffer
      from a high ratio of recurrence after liver transplantation (LT). Lenvatinib, as a novel
      targeted drug, has shown an excellent effect in the treatment of advanced HCC, but there is
      no study on its effect in preventing HCC recurrence in the patients undergoing
      transplantation. Therefore, to evaluate the role of adjuvant lenvatinib in preventing
      recurrence of high-risk LT recipients with HBV-related HCC, the investigators retrospectively
      analyzed 23 high-risk patients consisting of lenvatinib group (n=14) and control group (n=9)
      with HBV-related HCC who underwent LT. Disease-free survival (DFS) and HCC recurrence of the
      two groups were compared. The adverse events (AEs) and drug tolerance of lenvatinib were
      evaluated.
    

Detailed description: 
      The investigators retrospectively reviewed 23 Chinese HCC patients with HBV infection, who
      underwent LT in our hospital from June 2018 to December 2019. All donor grafts were allocated
      by the China Organ Transplant Response System. All these patients were diagnosed by histology
      and were defined as "high-risk" for recurrence.

      The participants were divided into lenvatinib group and control group according to their
      willingness to take lenvatinib as adjuvant therapy after LT. Of the 23 patients, 14 pantients
      in lenvatinib group began to take lenvatinib about a month after LT except for routine
      treatment, while the other 9 patients in control group received routine treatment and
      follow-up after transplantation. Clinical data and demographic characteristics was obtained.
      This study was conducted according to the 1975 Declaration of Helsinki and approved by Ethics
      Committee of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      (No. XHEC-D-2020-068). All patients enrolled in this study provided informed consent.

      Usage of lenvatinib and immunosuppressants The participants in lenvatinib group received oral
      lenvatinib (Eisai, Japan) 12 mg/day (for bodyweight (BW) ≥60 kg) or 8 mg/day (for BW <60 kg)
      in 28-day cycles until HCC recurrence or serious adverse events (SAEs) or voluntary
      withdrawal. Dose interruptions followed by reductions for lenvatinib-related toxicities (to 8
      mg and 4 mg/day, or 4 mg every other day) were permitted. All 14 patients took lenvatinib for
      more than 3 cycles.

      The induction immunosuppression strategies for all participants enrolled in the study
      involved IV infusion of 20mg of basiliximab within 2 hours prior to operation and a second
      dose 4 days later, oral tacrolimus started on the fourth day after LT at a dose of 0.04mg/kg
      (BW) and adjusted according to its plasma concentration, taking mycophenolate mofetil (MMF)
      from the next day after surgery at a dose of 500mg/kg(BW), and rapid withdrawal of
      glucocorticoids with the initial dose of 500mg. Maintenance immunosuppression which was
      started about one month after LT included sirolimus (4 mg/M2 per day) plus oral tacrolimus
      with the plasma concentration maintained at 5-8 ng/ml.

      All patients were followed up monthly within six months after LT and every three months
      within two years. During each follow-up, complete blood count, urinalysis, serum AFP level,
      liver and kidney function test, and blood concentration of FK506 were recorded. Chest and
      abdominal computed tomography was implemented at 3 months, 6 months, 12 months, and annually
      thereafter. Other radiological examinations such as radionuclide bone scan, magnetic
      resonance imaging (MRI) and positron emission tomography (PET) were obtained when local
      recurrence or distant metastasis was suspected.

      The DFS was defined as the period between the day of LT and the day of HCC recurrence
      confirmed by imaging, while the OS was defined as the duration from LT to death of patients
      for any reason or to end of follow-up. Common terminology criteria for adverse events version
      5.0 (CTCAE V5.0) was used to assess the AE during oral administration of lenvatinib. The
      FK506 dosage and blood concentration of each patients in the first six months after liver LT
      was recorded for evaluate the influence of lenvatinib on the immunosuppressive therapy.

      Mean and standard deviations were used for descriptive statistics. The patient
      characteristics in each group were compared by one-way ANOVA and chi-square tests. Repeated
      measures analysis of variances was used for comparing the difference of FK506 dosage and
      blood concentration between two groups. The OS and DFS were statistically analyzed by the
      Kaplan-Meier method. Statistical significance was set at P<0.05. All statistical analyses
      were performed using SPSS software Version 10.0.
    

Intervention name(s): Lenvatinib
Intervention type(s): Drug
Intervention description(s): The patients in lenvatinib group received oral lenvatinib (Eisai, Japan) 12 mg/day (for bodyweight (BW) ≥60 kg) or 8 mg/day (for BW <60 kg) in 28-day cycles until HCC recurrence or serious adverse events (SAEs) or voluntary withdrawal. Dose interruptions followed by reductions for lenvatinib-related toxicities (to 8 mg and 4 mg/day, or 4 mg every other day) were permitted. All 14 patients took lenvatinib for more than 3 cycles.
Intervention MeSH terms: Lenvatinib
Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        The cohorts in the study involved the patients who underwent liver transplantation for
        HBV-related HCC and were diagnosed as "high-risk" for recurrence according the above
        criteria.
      
Keywords: Hepatocellular Carcinoma; liver transplantation; lenvatinib; adjuvant therapy