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Real-world evidence of anlotinib in patients with advanced hepatocellular carcinoma and clinical role of α-fetoprotein
Background
Anlotinib, a novel multi-targeting tyrosine kinase inhibitor (TKI), has been investigated in a variety of malignant tumors and has shown efficacy in clinical trials for hepatocellular carcinoma (HCC). This study was designed to compare the efficacy of anlotinib versus some other protein kinase inhibitors (PKIs) as a first- or second-line therapy for advanced or metastatic HCC, and to identify the early predictive biomarkers for treatment response.
Methods
158 patients with a diagnosis of locally advanced or metastatic HCC receiving PKIs agents were retrospectively enrolled in this study. Patients treated with anlotinib were assigned to anlotinib group, while those receiving other common targeted drugs (sorafenib, lenvatinib, regorafenib, apatinib) were assigned to other PKIs group. All patients in anlotinib group received treatment at a dose of 12 mg on day 1 through 14 of a 21-day cycle. Patients were regularly followed-up by the investigators. Radiological imaging was done for all patients every 6 weeks after the first intervention dose. Laboratory test results were collected from the time of drug assignment to 30 days following treatment discontinuation. The efficacy of the treatment was assessed by the tumor response and survival. The primary end point was overall survival (OS).
Results
Between August 6, 2013 and October 18, 2021, 158 eligible patients were enrolled after PSM analysis. 54 were assigned to anlotinib and 104 were assigned to other PKIs. Median OS for anlotinib group was 14.8 months (95% CI: 13.6-16.2 months) versus 11.7 months (95% CI: 10.1-13.4 months) for other PKIs group (p=0.005). The median PFS was 5.7 versus 5.1 months (P=0.100). Subgroup analyses demonstrated a trend of superior OS benefit with anlotinib over other PKIs was consistently observed across most predefined subgroups. 24 or 30 patients were treated with anlotinib as first- or second-line therapy in anlotinib group. The number of patients treated with other PKIs as first- or second-line therapy was 51 or 53. In first-line therapy, anlotinib was not associated with a significantly longer PFS or OS than other PKIs. Anlotinib only exhibited superior OS versus other PKIs in second-line therapy. Hepatic biochemical markers were used to investigate early predictors for disease control. A multivariate analysis identified AFP response (a reduction in AFP of ≥40% from baseline) as an independent predictor of disease control in patients undergoing anlotinib treatment (P=0.001).
Conclusions
We performed in-depth analyses to determine whether anlotinib could show superior clinical outcomes over other PKIs in both first- and second-line therapy. For first-line therapy, mPFS was 5.0 months with anlotinib and 4.0 months with other PKIs (P=0.144), and mOS was 20.0 vs. 15.0 months (P=0.077). For second-line therapy, PFS was not improved either. Only mOS (13.0 vs. 10.0 months, p=0.001) were improved with anlotinib versus other PKIs. We separated patients with anlotinib into AFP response (a reduction in AFP of ≥40% from baseline) group and non-response group. Two groups show different DCR (P=0.001).
Legal entity responsible for the study
The author.
Funding
This study was supported by the State Key Project on Infection Diseases of China (Grant No. 2017ZX10201021-007-003), the National The capital health research and development of special (2018-1-4021), the National Natural Science Foundation of China (81972311, 82002611), CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant no. 2017-12M-4-002), the Non-profit Central Research Institution Fund of Chinese Academy of Medical Sciences (2019PT310026) and Sanming Project of Medicine in Shenzhen (No. SZSM202011010).
Disclosures
All authors have declared no conflicts of interest.
