Apatinib for metastatic breast cancer in non-clinical trial setting: Satisfying efficacy regardless of previous anti-angiogenic treatment

Abstract

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. This study aimed to evaluate the efficacy and safety of apatinib in metastatic breast cancer (MBC) under non-clinical trial setting, and to study the impact of previous antiangiogenic treatment to the efficacy of apatinib. 52 MBC patients treated with apatinib under non-clinical trial setting in Fudan University Shanghai Cancer Center between January 1st 2015 and October 1st 2016 were included. All patients were included in time-to-treatment failure (TTF) analysis, while 45 patients were enrolled for progression-free survival (PFS) and overall survival (OS) analysis because 7 of the patients with treatment discontinuation due to intolerable toxicities had too short time for efficacy assessment. Impact of previous exposure to antiangiogenic treatment and other factors to patients' survival were analyzed by Log-rank analysis and Cox multivariate analysis. The median PFS, median OS, and median TTF were 4.90 (95% confidence interval [CI] 3.44 - 6.36), 10.3 (unable to calculate 95% CI), and 3.93 (95% CI 1.96 - 5.90) months, respectively. Previous treatment of bevacizumab did not affect the efficacy of apatinib. Previous exposure to anthracycline, age of 60 years or older and palmar-plantar erythrodysesthesia syndrome were independent predictors for prolonged PFS. Discontinuation of treatment was more common in age group of 60 years or older than that in younger group, although the difference was not significant. Although toxicities were generally managable, a previously unrecorded grade 3~4 adverse event of dyspnea has been observed. This study confirmed the encouraging efficacy and manageable safety of apatinib on pretreated MBC patients in non-clinical trial setting. For the first time to our knowledge, this study found that previous treatment of bevacizumab did not affect the efficacy of apatinib, and reported an undocumented severe adverse effect of dyspnea.

Apatinib, a novel VEGFR-2 tyrosine kinase inhibitor, for relapsed and refractory nasopharyngeal carcinoma: data from an open-label, single-arm, exploratory study

“…In our study, most cases of hypertension, proteinuria, and hand-foot syndrome were of grades 1 and 2, with incidences of 56.86%, 49.02%, and 52.94%, respectively. These findings were generally consistent with the results of previous studies on other solid cancers [26,27]. It is worth noting that one patient showed severe hemorrhinia, possibly related to the treatment, which could indicate that VEGFR inhibitor drugs may increase bleeding risk in patients.…”

Apatinib Monotherapy for Chemotherapy-Refractory Metastatic Colorectal Cancer: A Multi-centre, Single-Arm, Prospective Study

“…The AEs observed in our study were either similar to those reported in previous studies of apatinib [10][11][12]19,20,[32][33][34][35] or to those of other VEGFR inhibitors 24,36,37 . Most grade 3 or 4 AEs were hypertension, proteinuria, HFS, thrombocytopenia, and mucositis oral, which was expected and tolerable for this patient population.…”

Progress in the treatment of solid tumors with apatinib: a systematic review

“…Moreover, it was found that preceding therapy with bevacizumab had no effect on the efficacy of apatinib. 45 …”