100 participants with advanced HCC who received sorafenib treatment from January 2019 to January 2021 in the Second Affiliated Hospital of Army Medical University were included in the study. The patient inclusion criteria were: (1) male or female patients aged ≥ 18 years; (2) HCC diagnosis was based on histological examination or the criteria of the American Association for the Study of Liver Diseases (AASLD) guidelines ; (3) liver function of Child-Pugh class A or B; (4) Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; (5) presence of unresectable or metastatic lesions; (6) acceptable heart, hepatic, renal and hematologic functions ; (7) estimated life expectancy ≥ 12 weeks; (8) at least one measurable lesion according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) . The following patients were excluded: (1) a previous history of sorafenib or any other PD-L1/PD-1 antagonist treatment; (2) other malignant tumors; (3) pregnancy or breastfeeding; and (4) Patients with incomplete follow-up data. The preoperative biochemical and radiological examinations were routinely performed in all patients. The study was approved by the Ethics Committee of the Second Affiliated Hospital of Army Medical University. Written consent was obtained from patients for the collection of clinical data for research purposes.
2.2 Treatment Protocol
The sorafenib-only group was administered sorafenib 400 mg orally twice daily. The combined-therapy group received camrelizumab 200 mg intravenously every 2 weeks in combination with sorafenib 400 mg orally once daily. When the patients experienced grade 3/4 treatment-related adverse events (AEs), the dose of sorafenib was reduced to 200 mg/day or discontinued until the AEs severity decreased to grade ≤ 2. Patients were treated until death, disease progression, unacceptable toxicity, consent withdrawn from the study.
2.3 Endpoints And Assessments
Demographic and clinical data were recorded and included age, gender, hepatitis B virus (HBV) carrier, Liver cirrhosis, ECOG performance score, and Child-Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein (AFP), total bilirubin (TBIL), albumin (ALB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count (PLT), white blood cell (WBC), prothrombin time (PT), tumor size, tumor number, macrovascular invasion, extrahepatic metastasis, and previous local regional therapy. The patients received CT or MRI evaluation at baseline and every 2 cycles of treatment (8 weeks) thereafter. Tumor responses were assessed according to the mRECIST and classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD).
The primary endpoint was progression-free survival (PFS). Secondary endpoints included over survival (OS), objective response rate (ORR), disease control rate (DCR) and AEs.
PFS was calculated as the time from the start of treatment to the date of disease progression or death due to any cause. OS was defined as the time from the start of treatment to the date of death due to any cause or the last follow-up. DCR was defined as the proportion of patients with CR, PR, and SD. ORR was defined as the proportion of patients with CR or PR. AEs were assessed and graded based on the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0).
2.4 Statistical Analysis
We performed Propensity score matching (PSM) analysis based on the following variables: age, sex, HBV carrier, liver cirrhosis, ECOG performance score, Child-Pugh stage, BCLC stage, AFP, tumor size, tumor number, macrovascular invasion, extrahepatic metastasis and previous local regional therapy. The continuous data were expressed as mean ± standard deviation or median with interquartile range and compared using t test or Mann–Whitney-Wilcoxon test. The categorical data were presented as frequency with proportion and analysed using Chi-square test or Fisher exact test. OS and PFS were estimated by the Kaplan–Meier method and log-rank test. P values < 0.05 were considered statistically significant. Statistical analyses and PSM were conducted using SPSS version 25.0 (IBM SPSS, Inc, Chicago, IL).