A Real-World Multicentre Retrospective Study of Low-Dose Apatinib for Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer

Abstract

Treatment options for human epidermal growth factor receptor (HER2)-negative breast cancer patients are limited in comparison to the HER2-positive patients, particularly for metastatic breast cancer patients. Apatinib is a small-molecule tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we reported the apatinib-based therapy data in HER2-negative metastatic breast cancer. Apatinib was taken at a dose of 250 mg orally once per day and combined with standard chemotherapy regimens. The PFS and OS of 128 patients were 4.7 months and 15.3 months, respectively. The objective response rate (ORR) and the disease control rate (DCR) were 22.7% and 80.5%, respectively. Patients with breast cancer susceptibility gene (BRCA) mutations were found to have a longer PFS and OS. Moreover, combination immunotherapy or paclitaxel-platinum regimens shared an improved response to other regimens. Most of the adverse effects (hypertension, anaemia, and hand-foot syndrome) were grade 1 to 2. Metastatic breast cancer patients could benefit from apatinib therapy at a low dosage, and the adverse effects are mild in real-world clinical practice. Furthermore, BRCA may be a putative biomarker for apatinib in HER2-negative breast cancer. Immunotherapy or paclitaxel-platinum regimens may be recommended to combine with apatinib therapy.

The efficacy and safety of apatinib in patients with heavily pretreated end-stage cancer: a retrospective study

“…In patients with end-stage cancer, the balance of adverse events and survival benefits should be considered. In the current study, a low dose of apatinib was effective and tolerable, and thus might be a potential choice for patients with end-stage cancer (40,41). This study has some limitations.…”

The efficiency and safety of low‐dose apatinib combined with oral vinorelbine in pretreated HER2‐negative metastatic breast cancer

“…In addition, we analyzed the factors that affect PFS and OS, and found that patients who were initially diagnosed in Stages III–IV or received as a third‐line treatment or beyond had a shorter PFS, while patients with DFS ≤24 months or with brain metastases had a shorter OS. Another real‐world study of low‐dose apatinib plus chemotherapy for mBC also showed that patients treated as third‐line or above had worse PFS (treated as third‐line or above vs. first‐ or second‐line: 3.5 vs. 5.1 months, p = 0.034) 44 . In the Phase II clinical study reported by Zhu et al., the PFS of patients treated ≥3 lines (5.2 months) was also shorter than that of patients treated <3 lines (6.1 months), but there was no statistically significant difference between the two group ( p = 0.875) 37 .…”

“…When apatinib combined with chemotherapy, the efficacy seems to be better. The ORR of apatinib combined with chemotherapy for mBC was 22.7%–35.5%, and the PFS was 4.7 months to 6.9 months 44–46 . A Phase II clinical trial about apatinib combined with oral vinorelbine for HER2‐negative mBC demonstrated that the ORR was 17.1%, the PFS was 5.2 months and the OS was 17.4 months 37 .…”

“…The ORR of apatinib combined with chemotherapy for mBC was 22.7%-35.5%, and the PFS was 4.7 months to 6.9 months. [44][45][46] A Phase II clinical trial about apatinib combined with oral vinorelbine for HER2-negative mBC demonstrated that the ORR was 17.1%, the PFS was 5.2 months and the OS was 17.4 months. 37 Compared to these results, the PFS and OS in our study were both longer and had a higher ORR.…”

A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer

“… 26 , 32 , 33 , 34 In a study of predictive biomarkers for antiangiogenic TKIs, patients with breast cancer susceptibility gene A mutations had a longer PFS and OS with apatinib. 35 In addition, in a small study in patients treated with anlotinib, the presence of TP53 and PIK3CA mutations were associated with significantly shorter PFS than that in patients without these mutations. 3 These data appear to contradict the current finding that PEG alterations increased the efficacy of anlotinib, possibly due to the smaller sample size and the different use of anlotinib in combination with eribulin.…”