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.