Abstract
BACKGROUND: Apatinib, a small-molecule tyrosine kinase inhibitor that selectively targets vascular endothelial growth factor receptor-2, has clinical activity in recurrent/advanced gynecological cancers. However, its efficacy in uterine malignancy remains unclear. This study aimed to determine the efficacy and safety of single-agent apatinib in patients with recurrent uterine malignancy. METHODS: This is a prospective single-center, single-arm, phase 2 study that enrolled patients aged 18-70 years with histopathologically confirmed recurrent endometrial cancer (EC) and recurrent uterine sarcoma (US), received at least 2 chemotherapy regimens, and an Eastern Cooperative Group performance status of 0-1. Apatinib (500 mg) was administered orally once daily. A treatment cycle was defined as 4 weeks. The patients were followed up every 2 cycles for tumor radiological assessment until disease progression. The primary endpoint was the overall response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were recorded throughout the treatment and within 30 days of the last study treatment and graded as per the National Cancer Institute Common Toxicity Criteria Version 4.0. RESULTS: A total of 33 patients (22 with EC and 11 with US) were enrolled between October 2018 and April 2021. Median follow-up duration was 11.7 months (interquartile range: 6.8-32.5 months). The patients received apatinib for a median of 4.79 cycles (range 2-13 cycles). In the EC and US cohorts, the ORRs were 27.2% [95% confidence interval (CI), 10.7% to 50.2%] and 9.1% (95% CI, 0.2% to 41.3%), the median PFS were 4.4 months (95% CI, 4.2 to 6.7 months) and 7.0 months (95% CI, 3.2 to 11.6 months), and the median OS were 11.7 months (95% CI, 6.8 months to not reached) and 18.1 months (95% CI, 9.2 months to not reached), respectively. The most common treatment-related AEs of all grades were hypertension (36.4%), proteinuria (33.3%), and hand-foot syndrome (30.3%). No treatment-related serious AEs or deaths occurred. CONCLUSIONS: To our knowledge, this is the first prospective study assessing the efficacy and safety of apatinib in patients with uterine malignancy. The results suggested that apatinib might be a potential treatment option for these patients.