Abstract
PurposeAs a novel small-molecule vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), Methylsulfonic apatinib (apatinib) exhibits a specific antitumor effect in various solid tumors via inhibition of angiogenesis. The present study was performed to evaluate the clinical efficacy and safety of apatinib in the treatment of advanced cholangiocarcinoma after failed gemcitabine-based chemotherapy.Patients and MethodsThis was a prospective open-label phase II trial (NCT03521219). A total of 32 patients, in whom gemcitabine-based first-line chemotherapy for advanced intrahepatic cholangiocarcinoma had failed, were consecutively enrolled in a prospective, open, exploratory, and single-center clinical trial from November 2017 to November 2018. They were treated with apatinib mesylate second-line monotherapy (orally, 500 mg per day for a cycle of 28 days) until progressive disease or unacceptable toxicity. Using Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST 1.1) and the Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE 4.0), the efficacy and adverse were evaluated, respectively. Kaplan-Meier method was used for survival analysis.ResultsTwenty-six patients were enrolled in full analysis set. At the end of follow-up, two patients were lost to follow-up, 24 of 26 patients in FAS were included in efficacy analyses. For the efficacy analysis set, the objective response rate (ORR) was 20.8% [95% confidence interval (CI): 9.24–40.47%] and the disease control rate (DCR) was 62.5% (95% CI: 112.86–387.14 days). One patient (4%) showed complete response (CR), 4 patients (17%) showed partial response (PR), 10 patients (41.7%) stable disease (SD), and 9 patients (37.5%) had progressive disease (PD). Meanwhile, apatinib therapy achieved the median progression-free survival PFS was 95 days (95% CI: 79.70–154.34 days), and the median OS was 250 days (95% CI: 112.86–387.14 days). Furthermore, univariate analysis revealed that age and tumor’s anatomic location significantly affected PFS (P < 0.05). The most common clinically adverse events (AEs) included myelosuppression (69.2%), hypertension (57.7%), proteinuria (46.2%). The AEs were mild, mainly in grade 1 or 2, and no toxicity-induced death occurred.ConclusionApatinib monotherapy is an effective and promising regimen for treating patients with advanced cholangiocarcinoma who experienced failure of gemcitabine-based chemotherapy.
Highlights
Cholangiocarcinoma is a highly malignant tumor with poor prognosis
From November 2017 to November 2018, a total of 32 patients with advanced cholangiocarcinoma were enrolled in our study and underwent apatinib therapy in the First Affiliated Hospital of Zhengzhou University
Thirty-two enrolled patients with advanced cholangiocarcinoma signed informed consent at the time we initiated this study, while six patients of them were excluded for withdrawing the consents prior to the first dose of apatinib
Summary
Cholangiocarcinoma is a highly malignant tumor with poor prognosis. Based on the anatomic site, it is divided to intrahepatic and extrahepatic cholangiocarcinoma. Non-specific symptoms of early cholangiocarcinoma, and lack of a satisfying marker or imaging technique for diagnosis [2, 3], many cases are already in the middle-late or advanced stage at the time of the treatment, and only suitable for systemic or palliative therapy. Only 10% of patients diagnosed at the early stage are eligible for surgical resection, which is why 5-year survival rate is very poor (only 5%) [4]. Gemcitabine combined with cisplatin or 5-fluorouracil as the “gold standard” for first-line treatment has been confirmed to improve survival, the median OS time is still shorter than 1 year. Given that there is no standard second-line treatment regimen at present, it is important to urgently establish novel therapeutic methods to improve survival time and achieve low toxicity
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