Interprovider Variation in Initiation of Bone-Modifying Agents for Patients With Prostate Cancer.

39 Background: Skeletal related events (SREs) are a set of morbidities resulting from metastatic bone disease, including pathologic fracture, spial cord compression, and others. Clinical practice guidelines recommend use of bone modifying agents (BMAs) to prevent SREs for patients with metastatic castration resistant prostate cancer (mCRPC), and against their use for SRE prevention in metastatic castration sensitive prostate cancer (mCSPC). Whether these drugs are delivered in a consistent, guideline-concordant manner across oncology providers has not been described. Methods: We conducted a multicenter, retrospective, cohort study of patients diagnosed with prostate cancer metastatic to bone during 2020-21. The sample included three large health systems in the US Northeast (two community-based networks and one academic cancer center), collectively employing > 1700 physicians and treating > 800 cases of high-risk and/or metastatic prostate cancer each year. Patient comorbidities, timing of emergence of CRPC, and dates of BMA initiation (zoledronic acid or denosumab) were ascertained via chart review. The primary outcomes were BMA overuse during CSPC (defined as BMA initiation prior to emergence of CRPC, among patients without a comorbid condition for which BMA therapy may be appropriate: osteoporosis, osteopenia, or osteoporotic fracture) and appropriate use during CRPC (defined as BMA initiation subsequent to emergence of CRPC). Results: There were 153 eligible patients, 51 from each health system. The median age was 72 years (IQR 65, 80), PSA at diagnosis was 110 (IQR 16, 720), and time from diagnosis to development of CRPC was 352 days (IQR 224, 453). At diagnosis, 14 (9%) patients had documented osteoporosis or osteopenia and 22 (14%) had prior osteoporotic fracture. Among 106 patients assessable for overuse during CSPC, 17 (16%) received BMA (ranging from 13%-21% among the three systems). Among 65 patients who developed CRPC, 32 (44%) had initiated BMA therapy prior to death or most recent follow-up. There was greater variation in use during CRPC, ranging from 22%-54% across the three systems. In time-to-event analysis, at 2 years after emergence of CRPC 52% of surviving patients had initiated BMA therapy (ranging from 30%-66% among the three systems). Conclusions: Overuse of BMAs appeared consistently low. However, guideline-concordant use for patients with metastatic CRPC may vary substantially among clinicians and healthcare systems. This degree of variation suggests that some patients with mCRPC who may benefit from BMA therapy do not receive it. Interventions to reduce these discrepancies and increase appropriate care may improve patient outcomes.

68 Background: Bone modifying agents (BMAs) do not prevent skeletal related events (SREs) among patients with metastatic, castration-sensitive prostate cancer (mCSPC). Within this population, BMAs are recommended for prevention of osteoporotic fractures but not for SRE prevention. Utilization patterns of BMAs among patients with mCSPC have not been described, and it is unknown whether these patients may receive BMAs intended for SRE prevention unnecessarily. We conducted this study to measure BMA use among mCSPC patients who are unlikely to have an indication for osteoporotic fracture prevention. Methods: We used linked SEER-Medicare data. Our cohort included men newly diagnosed with de-novo stage IV prostate adenocarcinoma during 2007-2015. We included those age > = 66 at diagnosis, who lived at least 60 days after diagnosis, had continuous enrollment in Medicare Parts A and B from 180 days prior to diagnosis through the outcome period and Part D from diagnosis through outcome period, and who received androgen deprivation or antiandrogen therapy after diagnosis. We excluded patients who had previously received BMAs, or who had existing osteoporosis, osteopenia, hypercalcemia, or prior bone fracture. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of prostate cancer diagnosis, during which time the development of castrate-resistant disease is unlikely to arise. We also assessed receipt of BMAs within 90 days of diagnosis as a secondary outcome. We used multivariable logistic regression to assess patient factors associated with BMA use. Results: Our sample included 2,998 patients. Median age at diagnosis was 77. 77% of patients were white, 12% were Black, and 11% were of other race/ethnicity. 77% of patients were treated in the physician office setting and 23% the hospital outpatient setting. Overall, 24% received a BMA within 180 days of diagnosis; 18% did within 90 days. BMA therapy was more common among patients treated in the hospital outpatient vs. physician office setting (OR 1.25, 95%CI 1.03-1.52). Age, race/ethnicity, comorbidity, and renal disease were not associated with likelihood of BMA therapy. There was substantial variation across the study period: 19% of patients received BMAs from 2007-2009 (19% zoledronic acid, 0% denosumab), and 29% from 2012-2015 (9% zoledronic acid, 21% denosumab). Conclusions: Use of BMAs among patients with mCSPC is common. In this cohort of mCSPC patients, who were unlikely to have a BMA indication for osteoporotic fracture prevention based on the absence of history of osteoporosis, osteopenia, or fracture, nearly one-quarter received BMAs. The increase in BMA use which occurred during the 2007-2015 study period appears to have been driven by increased utilization of denosumab following its approval in 2010. Use of BMAs in patients with mCSPC without a need for osteoporotic fracture prevention may constitute overuse.

6582 Background: Skeletal related events (SREs) are a known complication for the 80% of men with metastatic prostate cancer who have bone metastases. Previous studies have demonstrated that bone modifying agents (BMAs) such as zoledronic acid and denosumab reduce SREs in men with metastatic castration-resistant prostate cancer who have bone metastases and are now recommended by national guidelines. We sought to investigate factors associated with use of BMAs in Veterans with CRPC across the Veterans Health Administration (VA). Methods: Using the VA Corporate Data Warehouse, consisting of aggregated medical record data from 130 facilities, we used an algorithm previously published to identify men with a diagnosis of castration-resistant prostate cancer (CRPC) based on rising prostate specific antigen (PSA) levels while on androgen deprivation therapy and who received systemic treatment for CRPC with one of the commonly used therapies: abiraterone, enzalutamide, docetaxel, ketoconazole between 2010 and 2017. To account for clustering among facilities, we used a multilevel multivariable logistic regression to determine the association of patient and disease-specific variables on the odds of a patient receiving a BMA after they started treatment for CRPC. Results: Of 4,998 patients with CRPC in our cohort, 2223 (44%) received either zoledronic acid or denosumab at some point after they were initiated on treatment for CRPC. After adjusting for other variables and accounting for a facility, the odds of receiving a BMA decreased by 3% for every additional year of age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.98), and decreased significantly with increasing comorbid conditions (OR 0.94, 95% CI 0.72-0.98 for Charlson Comorbidity Index [CCI] of 1; OR 0.69, 95% CI 0.59-0.81 for CCI 2+). Patients who were Black had 25% lower odds of receiving a BMA than patients who were White (OR 0.75, 95% CI 0.65-0.87). PSA at time of CRPC treatment start had a small but not significant effect on receipt of a BMA (OR 1.04, 95% CI 1.00-1.08) for every unit increase of PSA on the log scale. PSA doubling time was not associated with receipt of a BMA. The presence of a diagnosis code for bone metastases was far lower than expected in this cohort of patients with CRPC (40.7%), and thus was not included in the model. We did not expect the presence of bone metastases to vary significantly among the other independent variables. Conclusions: Despite most patients with CRPC historically having bone metastases, less than half of patients with CRPC received a BMA. Patients who are older, had more comorbidities, or were Black were less likely to receive a BMA after starting treatment for CRPC. Understanding factors that lead to different patterns of treatment can guide initiatives toward more guideline-concordant care.

Comparative Analysis of Genomic Alterations across Castration Sensitive and Castration Resistant Prostate Cancer via Circulating Tumor DNA Sequencing.

12 Background: Bone modifying agents (BMAs) prevent skeletal related events among patients with castration-resistant prostate cancer (mCRPC) and bone metastasis, but not among patients with castration sensitive prostate cancer (CSPC). However, approximately 1/3 of Medicare patients with CSPC receive BMAs unnecessarily, and the costs to Medicare resulting from this overuse have not been assessed. Methods: We used linked SEER registry and Medicare claims data for persons diagnosed with stage IV prostate adenocarcinoma during 2011-2015, identified those who subsequently received a cancer therapy used exclusively for mCRPC, and measured 1) the number of doses of zoledronic acid and denosumab received between diagnosis and initiation of mCRPC therapy and 2) presence of patient comorbidities which may warrant BMA therapy for fragility fracture prevention (eg., osteoporosis, osteopenia). We estimated excess BMA costs to Medicare by assessing the proportion of patients who received BMA therapy during their CSPC interval and did NOT have an indication for fragility fracture prevention, using the Medicare fee schedule for drug prices. We estimated adverse event costs using event frequency and costs estimates drawn from the peer-reviewed literature. The modeled outcome was the cost to Medicare from excess BMA use for the cohort of patients diagnosed with stage IV prostate cancer each calendar year. We conducted one-way sensitivity analysis for each model input by using the highest and lowest estimates available from peer-reviewed sources, monthly vs. every-three-month dosing frequencies for both drugs, and by +/-20% for all other inputs. Results: The median time from diagnosis to initiation of CRPC therapy was 387 days (IQR 253,573), during which time 42% received >=1 dose of denosumab (mean doses = 7) and 18% received >=1 dose of zoledronic acid (mean doses = 7). The estimated, annual excess BMA cost to Medicare was $45,392,377, comprised of $43,303,078 and $45,512 in drug costs for denosumab and zoledronic acid, respectively, and $1,625,869 and $419,917 in adverse event costs, respectively. The estimate was most sensitive to denosumab administration schedule (monthly vs. every-three-month) [estimate range: $29,487,144 - $101,060,692] and the duration of CSPC [estimate range: $37,853,180 - $101,754,921]. Conclusions: BMA overuse in CSPC incurs substantial cost to Medicare, largely due to denosumab drug costs. Our sensitivity analyses suggest we may overestimate costs if denosumab dosing frequency is now lower than during our observation period (eg., if more providers now use 3-month dosing), and we may underestimate costs if patients now experience CSPC for a longer duration (a plausible consequence from the introduction of ARSi therapy for CSPC in the post-LATITUDE era). Avoidable costs and toxicity may be reduced by greater adherence to guideline-concordant use of BMAs.

e18878 Background: Bone metastases occur in up to 90% of men with metastatic prostate cancer and cause skeletal-related events (SREs) such as fracture and spinal cord compression. Although bone modifying agents (BMAs) have been shown to decrease the risk of SREs in men with metastatic castration-resistant prostate cancer (mCRPC), BMAs are not widely used in this patient population. In this retrospective study, we report the prescribing patterns of BMAs and predictors of BMA use in a large national cohort. Methods: We used the VA corporate data warehouse to identify patients with mCRPC who were treated with first-line mCRPC therapy (abiraterone, enzalutamide, docetaxel, or ketoconazole) between 2010 and 2017. BMA prescribing frequency and patterns were analyzed. Multivariable regression analysis was used to evaluate clinical and disease-specific factors associated with BMA use which are presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). Results: In the final cohort of 4,079 patients, the median age at mCRPC diagnosis was 73 years (IQR 66-81). 29% of patients in the cohort were Black. Diagnosis codes identified bone metastases at mCRPC diagnosis in 48% of the cohort (ICD-9 and 10 coding for sites of metastases are known to underestimate the actual incidence of metastases). Only 48% of patients received a BMA following initiation of treatment for mCRPC, 47% of which had already received a BMA 6 months prior to mCRPC diagnosis. For those who were new BMA starts, the median time to BMA administration from mCRPC treatment was 3.4 months (IQR 1.2-8.8). Factors associated with BMA use were having an ICD-9 or 10 diagnosis code for bone metastases at time of mCRPC treatment (OR 1.28, 95% CI 1.10-1.48), concurrent corticosteroid use (OR 1.90, 95% CI 1.53-2.38), and docetaxel use as first-line mCRPC therapy (OR 1.78, 95% CI 1.45-2.18). Factors associated with decreased BMA use were Charlson comorbidity index score of ≥ 2 (OR 0.75, 95% CI 0.62-0.90), advancing age (OR 0.86 per 10 years, 95% CI 0.79-0.94), and decreased eGFR (eGFR 30-59, OR 0.81, 95% CI 0.68-0.96; eGFR 0-29, OR 0.23, 95% CI 0.14-0.37). Having a diagnosis code for a SRE before mCRPC diagnosis (e.g., bone fracture and cord compression) did not impact BMA use, but the incidence of those events was low. Conclusions: Less than half of this VA cohort received a BMA after starting therapy for mCRPC. Key factors associated with BMA use were corticosteroid use and first-line docetaxel use, which likely represented more aggressive disease. Notably, patients who were older and had more comorbid conditions were less likely to receive a BMA despite being highest risk for frailty and SREs. Future quality improvement efforts aimed at increasing BMA use may address the needs of the geriatric mCRPC patient population.

68 Background: NCCN Guidelines recommend the use of bone-modifying agents (BMAs) to prevent skeletal-related events (SRE) for patients with castrate-resistant prostate cancer (CRPC) and bone metastasis, but not for castrate-sensitive prostate cancer (CSPC). Prior studies have identified both underuse of BMAs for CRPC and overuse for CSPC, but the clinical circumstances underlying these apparent gaps in care are unknown. Methods: Qualitative interview study, with physicians who treat prostate cancer within an academic cancer center and an affiliated network of community-based practices. Using a semi-structured interview guide, an experienced moderator probed participants’ experiences and perceptions around NCCN Guidelines recommendations, guideline adherence and non-adherence, and barriers to adherence. Interviews also probed participants’ views of potential interventions to promote guideline-concordant BMA use. Participants used Likert-scale items to rate the likely effectiveness of each intervention in influencing BMA practice patterns. They also identified the 3 most helpful interventions for reducing BMA underuse and overuse separately. Results: 19 physicians were invited, of whom 15 agreed to participate; 1 physician did not respond to some questions as outside scope of practice. All were aware of the recommendation for use of BMAs in CRPC. 14% (2/14) were unaware of the recommendation against BMA use for CSPC; an additional 29% (4/14) believed that BMA use could be appropriate for CSPC depending on the burden of bony metastatic disease. 36% (5/14) were unaware of recommendations for baseline DEXA scan and BMA for patients with low bone mineral density. The most commonly reported barriers (occurring “often” or “sometimes”) to BMA use for CRPC were obtaining dental clearance (11/15) and insufficient time in clinic (6/15). The interventions perceived as most helpful to reduce underuse for CRPC were dental navigation (11/15) and EMR-based guidance (9/15). The interventions identified as most helpful to reduce overuse for CSPC were peer-to-peer education (14/15) and EMR-based guidance (13/15). Conclusions: Among physicians treating prostate cancer in our study, there was incomplete awareness of guideline recommendations for screening and treatment of low bone mineral density, and against BMA use for SRE prevention in CSPC. Dental navigation, peer-to-peer education, and EMR-based guidance were preferred implementation strategies to reduce underuse and overuse of BMAs.

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.

Guidelines recommend bone-modifying agents (BMAs) for patients with castrate-resistant prostate cancer (CRPC) and bone metastasis, but not for castrate-sensitive prostate cancer (CSPC). Physicians beliefs and practices regarding BMA therapy are poorly understood. This was a qualitative interview study with embedded Likert-scale elements. Study participants were physicians who treat prostate cancer, located within an academic cancer center or an affiliated community-based network. Participants were asked about their experiences and practice patterns regarding BMA therapy. Participants used Likert-scale items to identify the most common barriers to guideline-concordant BMA use and the most effective potential interventions. Participants were subsequently asked to rank the three most common barriers and the three most effective interventions to reduce underuse (for CRPC) and overuse (for CSPC). Nineteen physicians were invited and 15 participated; one physician did not answer some questions as outside of their practice scope. All were aware of the recommendation for BMAs in CRPC. 14% (2/14) were unaware of the recommendation against BMA use for CSPC; an additional 29% (4/14) believed that BMA use could be appropriate for CSPC depending on the metastatic disease burden. 36% (5/14) were unaware of recommendations for screening and treatment of low bone mineral density. The most common barriers (occurring "often" or "sometimes") were obtaining dental clearance (11/15) and insufficient clinic time (6/15). The interventions identified as most effective to reduce underuse were dental navigation (11/15) and electronic medical record (EMR)-based guidance (9/15). The interventions identified as most effective to reduce overuse were peer-to-peer education (14/15) and EMR-based guidance (13/15). Awareness of guideline recommendations for screening and treatment of low bone mineral density and against BMA use for CSPC was good, but not complete. Dental navigation, peer-to-peer education, and EMR-based guidance were preferred intervention strategies to improve guideline-concordant use.

55 Background: Bone modifying agents (BMAs) prevent skeletal related events (SREs) among patients with metastatic, castrate-resistant prostate cancer (mCRPC) involving the bone. The utilization of BMAs among patients with mCRPC and bone metastasis has not been well defined, and the number of patients who may benefit but are undertreated is not known. We conducted this study to measure patterns of BMA among mCRPC patients. Methods: We used linked SEER cancer registry and Medicare claims data. Our cohort included men newly diagnosed with de-novo stage IV prostate adenocarcinoma during 2007-2015, with followup through 2016. We included those age > = 66 at diagnosis, had continuous enrollment in Medicare Parts A and B from 180 days prior to diagnosis through the outcome period and Part D from diagnosis through outcome period, and who received androgen deprivation therapy. We further limited the cohort to those who subsequently received a CRPC-defining therapy (eg., abiraterone, sipuleucel-T, docetaxel if occurring prior to CHAARTED trial results). We grouped the cohort according to those who did vs. did not have evidence of bone metastasis in claims. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of initiating a CRPC-defining therapy. Among patients who received BMAs after initiating CRPC therapy, we further characterized the time at which they first initiated a BMA. Results: Our sample included 1,303 patients, of which 85% had evidence of bone metastasis. Overall, 58% received a BMA within 180 days of initiating a CRPC-defining therapy. 66% of patients with evidence of bone metastasis received BMAs, compared to 16% of those without evidence. Of patients who received BMAs, 38% first received BMAs between 90 days prior to starting CRPC therapy and 180 days after; the remaining 62% were previously receiving BMAs during the castrate-sensitive phase of disease. Among patients with evidence of bone metastasis who initiated CRPC-defining therapy in 2007-2009, 65% received BMAs; this proportion was 69% and 64% for those began CRPC therapy during 2010-2013 and 2014-2016, respectively. Conclusions: Approximately two-thirds of patients with mCRPC and bone metastases received BMAs within 180 days of initiating a CRPC-defining therapy. In most cases BMA therapy was initiated while patients still had castrate-sensitive disease, for which BMAs are indicated only at lower doses for the prevention of osteoporotic fractures. Further work is needed to understand whether real-world dosing is in line with clinical indications, and whether the one-third of patients who did not receive BMA therapy appropriately reflects the proportion of patients with contraindications. Further work is also needed to characterize patient and provider factors associated with appropriate BMA use.

The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with abiraterone acetate plus prednisone (AAP) remains unclear. To investigate the association between BMA use and the outcomes of patients with mCSPC receiving AAP. In this cohort study, a post hoc analysis of individual participant data from the LATITUDE trial was performed. The LATITUDE trial, a phase 3 randomized clinical trial, aimed to assess the efficacy of AAP and androgen deprivation therapy (ADT) vs dual-placebo and ADT in patients with high-risk mCSPC (data cutoff, August 15, 2018). Eligible patients had newly diagnosed prostate cancer with metastases and at least 2 of 3 high-risk factors (Gleason score ≥8, presence of ≥3 lesions on bone scan, or presence of measurable visceral metastasis). The trial was conducted at 235 sites in 34 countries. Data for the present study were evaluated from July 18 to September 23, 2023. Use of BMAs was defined as the administration of bisphosphonates and denosumab within 90 days before and after randomization. The primary outcomes were time to skeletal-related events (SREs) and overall survival (OS). An SRE was defined as a clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery involving bone. Differences in these outcomes were examined using the restricted mean survival time from inverse probability of treatment weighting-adjusted Kaplan-Meier curves, estimated until the last event was observed (longest time observed, 63.9 months). Treatment × covariate interactions were analyzed using weighted Cox proportional hazards regression models for the total cohort. In the total cohort of 1199 patients (956 [79.7%] younger than 75 years), 597 (49.8%) received AAP and ADT, including 474 (79.4%) younger than 75 years and 384 (64.3%) with more than 10 bone metastases (AAP cohort); 602 (50.2%) were treated with dual placebo and ADT, including 482 (80.1%) younger than 75 years and 377 (62.6%) with more than 10 bone metastases (ADT cohort). In the AAP cohort, 132 patients (22.1%) received BMAs, while in the ADT cohort, 131 (21.8%) did. Zoledronic acid was the most frequently administered BMA in both the AAP (93 [70.5%]) and the ADT (88 [67.2%]) cohorts. During the median follow-up of 51.8 (IQR, 47.2-57.0) months in the AAP cohort, BMA use was associated with a longer time to SRE (difference, 7.8 [95% CI, 4.2-11.3] months) but not with OS (difference, 1.6 [95% CI, -2.5 to 5.8] months). In the ADT cohort, BMA use was associated with both time to SRE (difference, 9.3 [95% CI, 5.2-13.3] months) and OS (difference, 5.5 [95% CI, 3.2-9.8] months). No evidence was found that the outcomes of BMA varied by AAP or ADT (hazard ratio for time to SRE, 0.99 [95% CI, 0.48-2.08]; P = .99 for interaction; hazard ratio for OS, 1.31 [95% CI, 0.88-1.96]; P = .18 for interaction). The findings of this cohort study suggest that use of BMAs was associated with a longer time to SRE in patients with high-risk mCSPC treated with ADT, with or without AAP, suggesting that BMA use might provide benefits to this population.

Bone-modifying agents (BMAs) do not prevent skeletal-related events among patients with castration-sensitive prostate cancer (CSPC), but many patients receive BMAs unnecessarily. The costs to Medicare from overuse have not been assessed. We used linked SEER-Medicare data 2011-2015 to measure the frequency and number of doses of zoledronic acid (ZA) and denosumab received during CSPC (between diagnosis and initiation of metastatic, castration resistant prostate cancer therapy). We estimated excess BMA among patients who received BMA therapy for CSPC and did not have an indication for osteoporosis fracture prevention. We used the Medicare fee schedule for drug prices and peer-reviewed sources to estimate adverse event frequencies and costs. Median CSPC duration was 387 days (IQR, 253-573), during which time 42% of patients received ≥one dose of denosumab (mean doses, 7) and 18% received ≥one dose of ZA (mean doses, 7). Thirty-eight percent of those receiving denosumab and 47% of those receiving ZA had a history of osteoporosis, osteopenia, spine or hip fracture, or hypercalcemia. The estimated, annual excess BMA cost to Medicare was $44,105,041 in US dollars (USD), composed of $43,303,078 USD and $45,512 USD in drug costs for denosumab and ZA, respectively, and $682,865 USD and $75,585 USD in adverse event costs, respectively. In one-way sensitivity analysis, the estimate was most sensitive to denosumab dosing frequency (estimate range, $28,469,237 USD-$98,830,351 USD) and duration of CSPC (estimate range, $36,823,311 USD-$99,015,908 USD). BMA overuse in CSPC incurs substantial cost to Medicare, largely because of denosumab drug costs. Excess costs may be reduced by greater adherence to guideline-concordant BMA use.

95 Background: Most pts with prostate cancer with bone metastasis experience symptomatic skeletal events (SSEs) [PMID: 23884473], leading to increased morbidity and mortality. BMAs have been approved since 2007 and are recommended in mCRPC to prevent SSEs in pts with bone metastases or a high risk of osteoporotic fracture. Herein, we sought to assess the real-world trends of BMA administration in pts with mCRPC. Methods: We used the de-identified nationwide Flatiron Health electronic health record (EHR)-derived database to extract pt-level data. Inclusion criteria: pts with mCRPC with available date of diagnosis of mCRPC and information on receipt of BMA. Pts were categorized into 2 cohorts based on BMA receipt (e.g., bisphosphonates, denosumab, teriparatide, romosozumab) or not. Treatment trends of BMA by year of mCRPC diagnosis were summarized using frequency and percentages. Baseline characteristics at the time of mCRPC diagnosis (age, race-ethnicity, practice type, insurance) were compared between cohorts using the Wilcoxon rank-sum and Chi-squared tests. Results: Of 24,105 pts with metastatic prostate cancer in the dataset, 14,112 with mCRPC were eligible and included. 7,990 (56.6%) received BMA while 6,122 (43.4%) did not. In BMA receipt cohort: median age was 75 (IQR 67 – 81), majority were White (61%), treated in community practice (87%) and had commercial health plan (80%). In BMA non receipt cohort: median age was 75 (IQR 68 – 82), majority were White (61%), treated in a community practice (78%), and had commercial health plan (76%). The use of BMA decreased over time from 56% in 2013 to 46% in 2024 (Table). Statistically significant differences existed between cohorts in race-ethnicity, practice type, and insurance (p < 0.001) and will be presented at the meeting. Conclusions: Despite recommendations to use BMAs in pts with mCRPC and bone metastasis or high risk of osteoporotic fracture, our findings reveal a low utilization rate of BMAs in mCRPC setting with a notable decline over time. This highlights the need to incorporate the use of BMAs in clinical practice and improve access to these agents. Trends by year of mCRPC diagnosis in receipt of the first BMA and frequency and percentage of each agent. Year 2013N = 549 2014N = 1035 2015N = 1223 2016N = 1345 2017N = 1441 2018N = 1346 2019N = 1469 2020N = 1380 2021N = 1352 2022N = 1393 2023N = 1196 2024N = 383 Receipt of BMA, n (%) 316 (56) 674 (65) 792 (65) 837 (62) 886 (61) 766 (57) 816 (56) 766 (56) 692 (51) 713 (51) 556 (46) 176 (46) Denosumab, n (%) 190 (60.1) 450 (66.8) 557 (70.3) 599 (71.6) 606 (68.4) 533 (70) 526 (64.5) 488 (63.7) 410 (59.2) 414 (58.1) 290 (52.2) 94 (53) Zoledronic acid, n (%) 120 (38) 220 (32.6) 228 (28.7) 233 (27.8) 270 (30.5) 225 (29) 281 (34.4) 273 (35.6) 277 (40) 295 (41.4) 258 (46.4) 82 (47) Teriparatide, other bisphosphonates, n (%) 6 (1.9) 4 (0.6) 7 (1) 5 (0.6) 10 (1.1) 8 (1) 9 (1.1) 5 (0.7) 5 (0.7) 4 (0.5) 8 (1.4) 0

BackgroundMost patients with prostate cancer experience symptomatic skeletal events, leading to increased morbidity and mortality. BMAs have been approved since 2007 and recommended in mCRPC to prevent SSEs in patients with bone metastases or high-risk of osteoporotic fracture. Herein, we sought to assess real-world trends of BMA administration in patients with mCRPC.MethodsWe used the de-identified nationwide Flatiron Health electronic health record-derived database to extract patient-level data. Eligibility: patients with mCRPC with available date of mCRPC diagnosis and information on receipt of BMA. Patients were categorized into 2 cohorts based on BMA receipt. Treatment trends of BMA by year of mCRPC diagnosis were summarized using frequency and percentages. Baseline characteristics at mCRPC diagnosis (age, race-ethnicity, practice type, insurance) were compared using the Wilcoxon rank-sum and chi-squared tests.ResultsOf 24,105 patients with metastatic prostate cancer, 14,112 with mCRPC were eligible and included. A total of 7,990 (56.6%) received BMA while 6,122 (43.4%) did not. BMA receipt cohort: median age was 75 (IQR 67-81), the majority were White (61%), treated in community practice (87%) and had a commercial health plan (80%). BMA non-receipt cohort: median age was 75 (IQR 68-82), the majority were White (61%), treated in community practice (78%), and had a commercial health plan (76%). Use of BMA decreased over time from 56% in 2013 to 46% in 2024 (Table 1).ConclusionsDespite recommendations to use BMAs in patients with mCRPC and bone metastasis or high-risk of fracture, our findings reveal a low utilization rate of BMAs in mCRPC with a notable decline over time. This highlights the need to incorporate BMAs in clinical practice.Table 1Trends of BMA usage over time (2013-2024).Year, n (%)2013 N = 5492014 N = 10352015 N = 12232016 N = 13452017 N = 14412018 N = 13462019 N = 14692020 N = 13802021 N = 13522022 N = 13932023 N = 11962024 N = 383BMA receipt316 (56%)674 (65%)792 (65%)837 (62%)886 (61%)766 (57%)816 (56%)766 (56%)692 (51%)713 (51%)556 (46%)176 (46%)Denosumab190 (60.1%)450 (66.8%)557 (70.3%)599 (71.6%)606 (68.4%)533 (70%)526 (64.5%)488 (63.7%)410 (59.2%)414 (58.1%)290 (52.2%)94 (53%)Zoledronic acid120 (38%)220 (32.6%)228 (28.7%)233 (27.8%)270 (30.5%)225 (29%)281 (34.4%)273 (35.6%)277 (40%)295 (41.4%)258 (46.4%)82 (47%)Teriparatide/other bisph.6 (1.9%)4 (0.6%)7 (1%)5 (0.6%)10 (1.1%)8 (1%)9 (1.1%)5 (0.7%)5 (0.7%)4 (0.5%)8 (1.4%)0

e24144 Background: Zoledronic acid (ZA) and denosumab are both bone-modifying agents (BMAs) approved for use in patients with bone metastases with breast or prostate cancer as well as patients who are receiving aromatase inhibitors (breast cancer) or androgen deprivation therapy (prostate cancer). There are various frequencies of administration, doses, and duration of these agents depending on indication and extent of disease. Currently there is data to show that ZA can be given every 3 months in patients with metastatic breast and prostate cancer, however, there is no data that clearly indicates that denosumab every 3 months is non-inferior to every 28 days. This study aimed to analyze current prescribing patterns of ZA and denosumab in metastatic breast cancer and metastatic castration resistant prostate cancer patients at The University of Chicago Medicine (UCM). Methods: This was a retrospective study of 80 patients who received at least one dose of ZA or denosumab between July 1st 2018 to June 30th 2019 from UCM outpatient oncology clinic for the purpose of treating metastatic breast cancer or metastatic castration resistant prostate cancer in conjunction with standard antineoplastic therapy. All included patients must have bone metastases. Patients were divided into four groups by disease state (breast or prostate cancer) and BMA agent (ZA or 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. Descriptive statistics were used for skeletal-related events (SREs) and BMA associated adverse effects. Results: Patients who received ZA achieved higher adherence rates (100% breast, 86% prostate) compared to patients that received denosumab (63% breast, 23% prostate). The most common reason for the lower adherence rate in denosumab groups was scheduling convenience. During the study period, there were 3, 0, 2 and 5 patients had SREs in the above four groups respectively. The predominant adverse event across all groups was hypocalcemia and two patients with prostate cancer on denosumab developed osteonecrosis of the jaw. The cost analysis showed using ZA as primary BMA agent might save up to 2.5 million dollars per year at UCM. Conclusions: The use ofZA was associated with higher adherence rates compared to denosumab. Implementing a pharmacy driven protocol for ZA use for patients with metastatic breast and prostate cancer may improve BMA regimen adherence rates and significantly reduce costs.