Abstract

Abstract Background: In 2019, a quality improvement (QI) research project was conducted at UChicago Medicine (UCM) to evaluate bone modifying agent (BMA) use for skeletal-related event (SRE) prevention in patients with metastatic breast cancer and metastatic castration-resistant prostate cancer. Denosumab was the preferred BMA agent at UCM in this setting. Compared to zoledronic acid (ZA), denosumab was associated with higher drug cost and lower adherence rate mainly due to the difficulty of maintaining the 4-weekly frequency. Studies have shown that ZA can be de-escalated from 4-weekly to 12-weekly for SRE prevention. There is still no convincing evidence to show that this de-escalated schedule can be applied to denosumab. One study evaluated the noninferiority of 12-weekly compared with 4-weekly denosumab suggested that the health-related quality of life was non-inferior (Clemons et al., 2021). However, the study was not powered to evaluate the statistical difference in SRE rates. Based on the results of the 2019 QI project, a BMA pathway was generated at UCM in September 2020 with the purpose of guiding physician prescribing patterns, improving adherence rate, and reducing drug costs. This pathway recommended using ZA as the preferred agent for SRE prevention instead of denosumab. Methods: This was a retrospective study that included 198 patients who had metastatic breast cancer and received at least one dose of ZA or denosumab from UCM outpatient oncology clinic for SRE prevention. All included patients must have bone metastases. 107 patients from the pre-implementation study period (July 1st, 2018 to June 30th, 2019) and 91 patients from the post-implementation study period (November 10th, 2020 to November 10th, 2021) were included. Patients were divided into four groups based on study time (pre- or post-implementation period) and BMA agent (ZA and denosumab). The primary outcome was BMA therapy adherence rate, which was defined by those who received greater than or equal to 80% of appropriately scheduled doses. Secondary outcomes included the percentage of patients on ZA or denosumab, SREs, BMA-associated adverse effects, and BMA cost. Descriptive statistics were used SREs and BMA-associated adverse effects. Results: The percentage of patients on ZA significantly increased from 12% to 64% after BMA pathway implementation (P< 0.0001). Denosumab use decreased from 88% to 36% (P< 0.0001). The overall BMA adherence rate including both ZA and denosumab patients during the post-implementation period was 68%, which was not significantly different compared to the overall adherence rate of 74% during the pre-implementation period (P=0.5461). The adherence rates in denosumab groups (63% in pre and 30% in post) were lower than in ZA groups (100% in pre and 90% in post). The most common reason for the lower adherence rates in denosumab groups was scheduling convenience. During the study period, there were 2, 0, 3, and 3 patients who had SREs in the above four groups respectively. The predominant adverse events among all groups were hypocalcemia and hypophosphatemia. The cost analysis showed using ZA as the primary BMA agent saved 1.1 million dollars of drug costs during the post-implementation study period at UCM. Conclusion: Implementing a BMA pathway encouraged the providers to choose ZA as the preferred agent for SRE prevention in metastatic breast cancer patients with bone metastasis, which dramatically reduced drug costs. The overall BMA adherence rate was not significantly improved with the implementation. The difficulty of maintaining a 4-weekly denosumab frequency continued to exist. Citation Format: Kun Lin, Jordan Baur, Sandeep Parsad, Heng Yang. Implementation of A Bone Modifying Agent Pathway at UChicago Medicine for Metastatic Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-06.

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