A Phase II, Single-Arm Study of Apatinib and Oral Etoposide in Heavily Pre-Treated Metastatic Breast Cancer

Abstract

Introduction: We performed this clinical trial to evaluate the efficacy and safety of apatinib and oral etoposide in patients with HER2-negative locally advanced or metastatic breast cancer (MBC).

Methods: Patients with HER2-negative MBC previously treated with anthracycline and taxanes and failed ≥1 prior chemotherapy regimens were recruited. The starting dose of apatinib was 500 and 425 mg in patients with ECOG scores of 0-1 and 2, respectively. The etoposide capsules were given at 50 mg/m2 on days 1 to 10 for 21 days. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.

Results: Thirty-one eligible patients were enrolled. The median follow-up time was 11 months. The median PFS for all patients was 6.9 months [95% confidence interval (CI) 6.0-7.9], and 6.9 months (95% CI 5.3-8.6) and 6.6 months (95% CI 1.4-11.7) for patients with apatinib 425 and 500mg once daily, respectively. The ORR was 35.5% (11/31). The DCR was 87.1% (27/31). The median OS was 20.4 months (95% CI 11.4-29.3). The median PFS of patients who had hypertension and proteinuria was longer than that for those without hypertension and proteinuria. The most common grade 3/4 treatment-related AEs were hypertension (12/31, 38.7%), fatigue (3/31, 9.7%), thrombocytopenia (3/31, 9.7%).

Conclusion: Apatinib combined with etoposide capsules is effective and tolerable in heavily pretreated, metastatic HER2-negative breast cancer patients. A lower apatinib dose provide equivalent efficacy and reduced toxicity.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT03535961" title="See in ClinicalTrials.gov">NCT03535961.

Keywords: HER2-negative; angiogenesis; apatinib; breast cancer; oral etoposide.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Hu, Zhu, Si, Yue, Wang, Wang, Ma, Xu and Yuan.

Figures

Figure 1

Clinical profile.

Figure 2

Waterfall plot for the best percentage change in target lesion size.

Figure 3

Kaplan-Meier graph for progression-free survival in all patients.

Figure 4

Kaplan-Meier graph for progression-free survival in patients who had hypertension (A) and proteinuria (B) (n=31). (A) Median progression free survival (PFS) in patients with hypertension was significantly longer than that in patients without hypertension [7.4 months (95% CI 6.0–8.4) versus 2.6 months (95% CI 2.2–3.0), hazard ratio (HR) 0.28 (95% CI 0.09–0.83), p = 0.022)]. (B) Median PFS was also significantly longer in patients with proteinuria than those without proteinuria [8.1 months (95% CI 2.4–13.9) versus 4.0 months (95% CI 0.1–7.9), HR 0.38 (95% CI 0.15–0.94), p = 0.036].