Safety and Efficacy of Long-Term Zoledronic Acid in Advanced Breast Cancer with Bone Metastasis in South China.

Qianyu Wang,Roujun Peng,Guifang Guo,Wenzhuo He,Liangping Xia,Xuxian Chen,Yuming Rong,Long Bai,Jinsheng Huang,Shousheng Liu,Zhaohui Ruan,Ying Guo,Chang Jiang,Bei Zhang,Huijiao Cao

doi:10.1155/2020/5670601

Qianyu Wang, Roujun Peng + Show 13 more

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https://doi.org/10.1155/2020/5670601

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Abstract

Background This retrospective study aimed to characterize the long-term (>24 months) safety profile of zoledronic acid (ZA). We aimed to investigate whether long-term ZA treatment had greater benefits than short-term treatment in patients from southern China with advanced breast cancer (ABC) with bone metastasis. Patients and Methods. A total of 566 metastatic breast cancer cases were included and divided into two groups according to the duration of ZA treatment. The included patients had at least one lytic bone lesion and had no skeletal-related events (SREs) prior to ZA therapy. The primary endpoint was to analyze the safety and long-term adverse effects, which covered osteonecrosis of jaws (ONJ), renal impairment, and hearing impairment. The second objective was to determine the efficacy of long-term ZA treatment by the incidence of SREs. Results Fifteen patients were diagnosed with ONJ (2.7%): nine in the short-term group (3.1%) and six in the long-term group (2.2%, P = 0.606). Five cases (0.9%) had renal function impairment: two in the short-term group (0.7%) and four in the long-term group (1.1%, P = 0.676). One patient (0.2%) in the long-term group had hearing impairment after 23 months of ZA treatment (0.4%, P = 0.482). In total, 103 cases in the short-term group (35.2%) and 138 cases in long-term group (50.5%) developed SREs (P < 0.001). The mean annual SRE rate was 0.3 in the short-term group (range, 0–3.1) versus 0.2 in the long-term group (0–1.0, P = 0.269). Subgroup analysis suggested that cases with non-load-bearing bone involvement and those who received systematic anticancer therapy without chemotherapy might benefit from long-term ZA treatment. Cox regression analysis indicated poor performance status, and nonvisceral organ involvement predicted high risk for SRE. Conclusions The extension of ZA treatment did not increase the long-term adverse events and reduced the annual incidence of SREs beyond 24 months. Although longer treatment of ZA over 24 months appeared to be safe, further prospective investigation is required.

Highlights

Bone is the most frequent metastatic site in advanced breast cancer (ABC), accounting for approximately 65% to 75% of metastatic cases [1]
zoledronic acid (ZA) is effective in minimizing bone loss and delaying the onset and reducing the risk of skeletalrelated events (SREs) [3,4,5,6,7,8]. e American Society of Clinical Oncology (ASCO) guideline recommends the use of ZA for breast cancer patients with lytic bone metastasis [9]
All eligible cases received more than 6 months of ZA treatment without a skeletal-related events (SREs) before ZA initiation and had complete clinical information and survival data. e exclusion criteria were as follows: (1) patients with other malignant carcinomas besides breast cancer; (2) patients who received any type of bone-modifying agent (BMA) other than ZA or ZA combined with another BMA; and (3) cases with incomplete clinical information or survival data

Summary

Introduction

Bone is the most frequent metastatic site in advanced breast cancer (ABC), accounting for approximately 65% to 75% of metastatic cases [1]. Bone lesions change their metabolism and mobility [2], which increases the risk of skeletal complications and has a detrimental impact on patients’ quality of life [1]. The risk of SRE increases as lifetime dilation [10] It is currently unknown how long metastatic bone patients are treated with ZA, guidelines suggest that patients should continue intravenous bisphosphonates until a substantial decline in their performance status is apparent [9, 11]. It has been reported that prolonged administration of bisphosphonates (pamidronate, ibandronate, or ZA) was effective in northern Chinese ABC patients with bone metastasis, there is currently no standard duration [9, 17]. e objective of this study was to explore the safety and efficacy of long-term (>24 months) compared to short-term (≤24 months) ZA treatment for breast cancer patients from southern China with bone metastasis

Patients and Methods

Results

Findings

23 Favor group A