Patients and Methods
Study design and patients
This is a single center retrospective study of patients who received
PD-1 inhibitor monotherapy with toripalimab, camrelizumab or sintilimab;
or combination therapy with other modes of cancer treatments. Patients
with chronic HBV infection, and radiologically or histologically
diagnosed HCC were eligible. The approval for this retrospective study
was obtained from the local institutional ethics committee. Written
consents were obtained from patients prior to their enrolment into this
study.
Dosage PD-1 inhibitor therapy
Toripalimab was given intravenously at 3mg/kg body weight or at a fixed
dose of 240mg every 2 weeks. Camrelizumab was given at a fixed dose of
200mg every 2-3 weeks intravenously. Sintilimab was given at a fixed
dose of 200mg every 3 weeks intravenously.
Assessments
Clinical and laboratory data were collected from all patients prior to
PD-1 inhibitor therapy. Clinical data included age, gender, Barcelona
Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group
(ECOG) performance and Child-Pugh score. In addition, imaging data were
collected based on abdominal computed tomography (CT) and/or magnetic
resonance imaging (MRI), including tumor size, number, vascular
invasion, and extrahepatic metastasis. Laboratory data included
alpha-fetoprotein (AFP), alanine aminotransferase (ALT), aspartate
aminotransferase (AST), albumin, total bilirubin (TBIL), hepatitis B
surface antigen (HBsAg), and prothrombin time (PT).
The patients underwent CT or MRI at baseline, 6-12 weeks after treatment
initiation, and about every 3 months thereafter. Efficacy of treatment
was measured by overall survival (OS) (defined as the interval between
the first dose of PD-1 administration until death or the last
follow-up), time to tumor progression (TTP) (defined as the time from
first checkpoint inhibitor administration until the date that tumor
progression was confirmed radiologically), and progression free survival
(PFS) (defined as the time from first checkpoint inhibitor
administration until radiological disease progression or death, whatever
came first). Treatment related adverse events (TRAE) were recorded at
every visit according to the US National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE v4.03) [33].
Tumor responses were evaluated according to the modified response
evaluation criteria in solid tumor (mRECIST) [34] : (1) Complete
response (CR), all enhanced imaging of the target lesions in the
arterial phase disappeared; (2) Partial response (PR), the total
reduction of the diameter of the target lesions (enhanced arterial
phase) was ≥30%; (3) Stable disease (SD), the diameter of the target
lesion did not reduce to that in PR and did not increase to that in
disease progression (PD); (4) Progressive disease (PD), the diameter of
the target lesion (enhanced imaging in the arterial phase) increased by
at least 20% compared with the baseline value, or new lesions appeared.
Statistical Analysis
Statistical analysis was performed in SPSS Statistics for Windows
(version 20.0, SPSS Inc., Chicago, IL, USA). Data were expressed as
counts and percentages for categorical variables such as those in
baseline characteristics, radiological tumor response and side effects.
Kaplan-Meier survival curves were plotted for all groups. All
statistical analyses were based on two-tailed hypothesis tests with a
significance level of p<0.05. Comparison between three PD-1
inhibitor groups were not performed due to the low sample size after the
cohort is subdivided.