Use Of Bone-modifying Agents Research Articles

Expert consensus on safety management of bone-modifying agents

Bone-modifying agents are a class of drugs that alleviate a series of bone-related events such as pain, pathologic fracture, spinal cord compression, and hypercalcemia caused by bone metastases, and currently include bisphosphonates and RANKL inhibitors. Due to the widespread use of bone-modifying agents, the adverse effects of them are gradually increasing and affecting patients' quality of life. The Breast Cancer Group, Chinese Medical Doctor Association, and the International Medical Society, Chinese Anti-cancer Association have organized relevant experts to focus on the treatment of bone metastases of advanced malignant tumors based on evidence-based medicine, discuss the management of adverse reactions to bone-modifying agents and form the consensus. Based on the first Expert Consensus on Safety Management of Bone-modifying Agents in China, this consensus added the definition of osteonecrosis of the jaw related to bone-modifying agents, the occurrence of adverse reactions of bone-modifying drugs reported in the literature, and summarized the clinical experience of clinicians in the management of adverse reactions in practice in recent years, and ultimately, the expert group members discussed and proposed reasonable suggestions to guide clinicians in the safety management of bone-modifying agents.

Bone-Modifying Agents in Patients With High-Risk Metastatic Castration-Sensitive Prostate Cancer Treated With Abiraterone Acetate

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.

Treatment of bone metastases from solid tumors with bone-modifying agents: a web survey of Italian oncologists investigating patterns of practice drug prescription and prevention of side effects

PurposeOptimal use of bone-modifying agents (BMAs) in patients with bone metastases from solid tumors is uncertain in some aspects: the drug choice; the planned treatment duration and long-term therapy; the prevention and management of possible side effects, including renal toxicity, hypocalcaemia, and medication-related osteonecrosis of the jaw (MRONJ).MethodsItalian oncologists were invited to fulfil a 24-question web survey about prescription of BMAs for bone metastases of breast cancer, prostate cancer, and other solid tumors. Prevention and management of side effects were also investigated.ResultsAnswers of 191 oncologists were collected. BMAs are usually prescribed at the time of diagnosis of bone metastases by 87.0% (breast cancer) and 76.1% (solid tumors except breast and prostate cancers) of oncologists; the decision is more articulated for prostate cancer (endocrine-sensitive versus castration-resistant). The creatinine level (32.3%), the availability of patient venous access (15.8%), and the type of primary neoplasm (13.6%) are the most reported factors involved in choice between bisphosphonates and denosumab. Zoledronic acid every 3 months was considered as a valid alternative to monthly administration by 94% of Italian oncologists. Oncologists reported a good confidence with measures aimed to prevent MRONJ, whereas uncertainness about prevention and management of hypocalcemia was registered.ConclusionItalian oncologists showed a high attitude in prescribing bisphosphonates or denosumab at the time of diagnosis of bone metastases, with a large application of preventive measures of side effects. Further studies are needed to investigate some controversial aspects, such as optimal drug treatment duration and long-term drug schedules.

Whole-cycle management norms of bone health in breast cancer

Bone health management of breast cancer runs through the whole cycle of patient treatment. During the process of adjuvant treatment for early breast cancer, clinicians should be pay attention to the prevention of bone loss caused by treatment. Adjuvant use of bone-modifying agents can help improve the prognosis of some patients, and patients with bone metastases should be given multidisciplinary comprehensive treatment and use bone-modifying agents to prevent the occurrence bone related adverse events. Therefore, no matter for the treatment of early or advanced breast cancer, it is necessary to manage bone health, formulate appropriate treatment strategies, and deal with adverse events of drugs. Good bone health management will help improve the quality of life and survival of patients. The breast cancer expert committee of the National Cancer Quality Control Center organized relevant experts to deeply explore the full cycle management of bone health in breast cancer based on Evidence-based medicine evidence. The risk classification and treatment strategy of cancer treatment-induced bone loss in early breast cancer, the applicable population and benefits of adjuvant treatment of bone modifying drugs, the diagnosis and treatment of bone metastasis in advanced breast cancer, and the treatment of adverse reactions of bone modifying drugs were elaborated in detail. We hope to guide clinicians to better deal with bone health problems in clinical practice by putting forward reasonable suggestions for patients with breast cancer.

Medication-related osteonecrosis of the jaws associated with the use of bone-modifying agents

The relevance of the study is associated with the widespread use of osteomodifying agents in patients with bone metastases and osteoporosis. Bisphosphonates and other osteo-modifying agents are widely used in oncology and prevention of age-related changes in the human bone system. The use, therapeutic effects and complications of therapy with osteo modifying agents are being investigated all over the world. However, the etiology and pathogenesis of drug-induced osteonecrosis of the jaws (MONCH) have not been fully studied, in this regard, the study of risk factors and mechanisms of its development remains relevant. New data on the etiology and pathogenesis of drug-induced osteonecrosis are presented. The literature review is carried out on the electronic resource PubMed.

Medication-related osteonecrosis of the jaws associated with the use of bone-modifying agents: new studies

The relevance of the study is associated with the widespread use of osteomodifying agents in patients with bone metastases and osteoporosis. A serious complication associated with the use of bisphosphonates and other osteomodifying agents is known — medical osteonecrosis of the jaws, but the pathogenesis of this disease has not been fully studied. With drug-induced osteonecrosis of the jaws in oncological patients with bone metastases, therapy with osteomodifying agents is suspended, which can cause a decrease in the patient's life span. This is due to the importance of prevention, early diagnosis, and rapid treatment of patients with drug-induced osteonecosis. The aim of the work was to analyze the studies carried out in 2021—2023 on new methods of diagnosis, treatment, prevention of medical osteonecrosis of the jaws. The literature review is based on the analysis of published studies according to the PubMed electronic resource.
 The analysis of the literature data showed that bisphosphonates and other osteomodifying agents are widely used in oncology and the profile of age-related changes in the human bone system. The use, therapeutic effects and complications of therapy with osteomonefying agents are being investigated all over the world. Cone-beam computed tomography remains the "gold standard" in the diagnosis of medicamental osteonecrosis of people. Antibiotic therapy is considered as an effective method of treatment. It is proposed to use hyperbaric oxygenation, laser treatment, bone resection under fluorescence control, photodynamic therapy, introduction of a biomaterial based on tricalcium phosphate, administration of teriparatide and atorvastatin as additional treatment methods. Regular dental examinations are the most effective means of preventing drug-induced osteonecrosis. The study of pathogenesis, new methods of therapy and prevention of drug-induced osteonecrosis of the jaws remains urgent.

Management of bone metastasis in prostate cancer.

Progression of bone metastases is the primary cause of death in prostate cancer, and skeletal-related events (SREs), including pathologic fractures, spinal cord compression, radiation, or surgery to bone can impair patients' quality of life. Over the past decade, the development of cytotoxic agents, androgen-receptor-axis-targeted therapies (ARATs), and radioligand therapies has prolonged overall survival of prostate cancer patients with bone metastases and reduced the risk of SREs. The use of bone-modifying agents has also contributed to the reduced risk of SREs. Initial use of a cytotoxic agent, docetaxel, or an ARAT agent with androgen deprivation therapy (ADT) is the current approach to metastatic castration-sensitive prostate cancer. However, there is no consensus on the optimal medication for upfront use in combination with ADT, or on specific patient selection. Recently, next-generation imaging modalities, such as whole-body magnetic resonance imaging and prostate-specific membrane antigen-positron emission tomography have been utilized to detect bone metastases at an early stage. In addition, metastasis-directed therapy, such as stereotactic body radiation therapy, has been attempted. In the future, patients with bone metastatic prostate cancer will be divided into subgroups and their treatment options will be tailored to their specific characteristics.

Barriers to guideline-concordant use of bone modifying agents for prostate cancer.

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.

Real-world variability in use of bone-modifying drugs for multiple myeloma by payer type.

129 Background: The use of bone-modifying agents (BMAs) in multiple myeloma is gold standard. Benefits include prevention of skeletal-related events, reduction in bone pain, and improved progression-free survival. Guidelines recommend that patients with active multiple myeloma receive a BMA for up to two years. Unfortunately, real-world data has shown undertreatment with delays in initiation, interruptions in dosing, and premature discontinuation. These gaps are more pronounced for Black patients. The objective of this study was to describe real-world BMA treatment patterns across different payer types: Medicaid, Medicare, and Commercial/Exchange. Methods: This was a retrospective observational study using oncology prior authorization data from multiple payers in the New Century Health (NCH) database. NCH is specialty risk management company who supported over 107,000 oncology patients in 2021. All patients with a diagnosis of multiple myeloma, as indicated by the treating provider’s office, were included who had a prior authorization request for anti-cancer therapy between January 1, 2021, and December 31, 2021. Use of BMA was defined as having ≥1 authorization request for zoledronic acid or denosumab any time in the prior 24 months. BMA use was also evaluated by payer: Medicaid, Medicare, or Commercial/Exchange. Results: A total of 4774 patients were identified as having active multiple myeloma from January 1, 2021, to December 31, 2021. Fifty-nine percent (59.6%) of patients had at least one authorization request for a BMA submitted by their treating provider any time in the preceding 24 months. While most of the identified patients had Medicare, when request for BMA was disaggregated by payer, meaningful differences were found. For patients with commercial or exchange coverage, 64.6% (281/435) had a BMA requested; for patients with Medicare coverage, 60.1% (2339/3890) had a BMA requested. However, for patients with Medicaid, only 51% (229/449) had a BMA requested. Conclusions: Like other studies, our findings highlight underuse of BMAs in multiple myeloma. Differences in request for BMA across payer types suggests variability in adherence to guidelines may be based on patient insurance. To achieve equitable outcomes, including for patients of lower socioeconomic status, targeted efforts must be put in place to ensure receipt of guideline-directed therapy. A strength of this study is the large population and diversity of patients from practices in 41 states with multiple payer types. However, our analysis is limited by several unknown factors such as patient contraindication to or declination of BMA in past that are not captured in the NCH database. This retrospective study, using a large real-world oncology database, highlights that many patients with multiple myeloma may not be receiving guideline-based BMA therapy and that there are meaningful differences depending on patient insurance type.

Statin type and survival of patients with metastatic castrate-resistant prostate cancer receiving abiraterone and enzalutamide: A nationwide retrospective cohort study.

50 Background: Studies have suggested that statin use is associated with prostate cancer mortality. However, uncertainties exist in how the solubility profile of statins impact cancer outcomes. Lipophilic statins have greater accessibility in extrahepatic tissues, which may lead to stronger inhibitory effects on cancer cells, whereas hydrophilic statins exhibit greater hepato-selectivity and therefore less likely to cause drug interactions and adverse events. Abiraterone (ABI) and enzalutamide (ENZ) are antiandrogen agents used in metastatic castrate-resistant prostate cancer (mCRPC). In this study, we sought to examine whether statin usage and lipophilicity of statins is associated with survival benefits in mCRPC patients receiving ABI or ENZ. Methods: We conducted a nationwide retrospective cohort study of the Veteran Affairs population. Patients with mCRPC who received statin therapy one year prior to initiation of either ABI or ENZ between 9/10/2014 and 6/3/2017 were included and followed until April 2020. Statins were categorized as lipophilic (atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin, pitavastatin) and hydrophilic (rosuvastatin and pravastatin). A cox proportional hazards model was used to estimate adjusted hazards ratio (aHR) with 95% confidence interval (CI) of overall survival after controlling for known prognostic factors including age, Charlson-Romano Comorbidity Index, use of bone-modifying agents, Body-Mass Index, and prostate specific antigen levels. Results: A total of 4919 patients (mean age 75.0 years) were included in our cohort. Of those, 969 patients (19.7%) received lipophilic statins and 452 patients (9.2%) received hydrophilic statins. After adjusting for known factors, statin use was not associated with improved overall survival (aHR 0.93; 95% CI 0.87 – 1.00). Similarly, the use of lipophilic statins (aHR 0.98; 95% CI 0.90 – 1.06) or hydrophilic statins (aHR 0.90; 95% CI 0.80 – 1.01) were not associated with improved overall survival in mCRPC. Conclusions: Our study found no differences in overall survival between mCRPC patients with statin use compared to those without statins. When analyzing statin lipophilicity, we saw a higher trend towards survival in the hydrophilic statin group compared to the lipophilic statin group, which contradicts the direct anticancer benefits of lipophilic statins, but neither group reached statistical significance. Further studies analyzing statin usage and types with specific outcome measures such as cardiovascular events, duration of antiandrogen therapy, and adverse events related to ABI or ENZ will support in optimal therapy choices for mCRPC.

Diagnosis and treatment of medication-related osteonecrosis of the jaws from an oncologist's perspectives

Along with the improvement of cancer treatment and the increasing use of bone-modifying agents, medication-related osteonecrosis of the jaw (MRONJ) has become more and more common, which may lead to reduce quality of life for patients and interrupt their regular tumor treatments. Being an oral condition in the maxillofacial region of patients associated with adverse side effect of certain bone-modifying agent related cancer therapies, MRONJ falls in a gray area between oncology and stomatology and can be challenging to treat and manage if standard clinical practice and care management guideline is not well established. Missed diagnosis and misdiagnosis of MRONJ become common when there is lack of elucidated diagnostic criteria and coordination in treatment planning between patient's oncologist and dentist. Patient's primary attending oncologist who initiates therapy with bone-modifying agent should be aware of MRONJ and well knowledgeable in best practices for preventing and managing MRONJ. With the focus on coordination of care in mind, an oral health assessment of the patient should be undertaken before initiating therapy and a dental treatment plan should be developed and implemented in coordination with the patient's dentist. Based on the systematic review of the 2019 "Medication-Related Osteonecrosis of the Jaw MASCC/ISOO/ASCO (Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology/American Society of Clinical Oncology) Clinical Practice Guideline", combined with clinical experience and academic research progress of related subject in recent years, from the perspective of an oncologist, the author summarizes how oncologists play a pivotal role in every step of the way from the initial cancer diagnosis, pre-cancer treatment assessment, care management during bone-modifying agent therapy, to the diagnosis, treatment, and management of MRONJ. The primary focus of the present article is to formulate optimized recommendations and provide guidance for multidisciplinary teams regarding best practices in the prevention and management of MRONJ in patients with cancer, in terms of early awareness, prevention, detection as well as implementation of effective treatment plan to improve clinical outcome and increase quality of life for the patients.

The awareness and practice of dentists regarding medication-related osteonecrosis of the jaw and its prevention: a cross-sectional survey

BackgroundAccurate documentation of a patient’s prior medication use and awareness of side effects associated with anti-osteoporotic agents can assist dentists to prevent medication-related osteonecrosis of the jaw. I aimed to determine the awareness of Korean dentists regarding medication-related osteonecrosis of the jaw and the duration of drug holidays they prescribe to patients who need to undergo various dental procedures.MethodsAn online, questionnaire-based survey was conducted among 1000 dentists registered in an online community in Korea. The following were determined: general characteristics; type of practice; recordkeeping regarding patients’ use of bone-modifying agents; requirement of a doctor’s referral letter; advice given regarding drug holidays of bone-modifying agents before dental surgery procedures; and experience with medication-related osteonecrosis of the jaw. Differences between dentists with and without experience in treating patients with medication-related osteonecrosis of the jaw were evaluated using the χ2 test.ResultsAlthough a relatively high proportion (293/1000, 29.3%) of dentists had experienced cases of medication-related osteonecrosis of the jaw, only 650/1000 (65.0%) routinely documented the type of bone-modifying agent used by patients and the duration of its use. Moreover, only 591/1000 (59.1%) dentists routinely requested referral letters from doctors before performing dental surgery on patients. Although the recommended period for a drug holiday differs for each drug, 533/1000 (53.3%) dentists did not make such a distinction. There was a statistically significant difference in the level of detail documented in terms of anti-osteoporotic drug use between dentists who had no experience in medication-related osteonecrosis of the jaw (707/1000) and those who had such experience (P = 0.007). There was a statistically significant difference in the length of drug holidays prescribed between dentists with and without prior experience with the condition (P = 0.001).ConclusionsThese results suggest that dentists do not respond consistently to patients' drug history prior to performing dental procedures. This implies the need for increased cooperation between dentists and physicians, as well as the development of targeted educational interventions for the dental profession, to reduce the risk of medication-related osteonecrosis of the jaw.Trial registrationNot applicable.

P09.13 Bone Metastases and Overall Survival in Patients with Metastatic Non-Small Cell Lung Cancer Treated with Pembrolizumab

Bone metastases (BM) and skeletal-related events (SRE) are a common cause of morbidity in patients with metastatic non-small cell lung cancer (mNSCLC). Data on the impact of BM on overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI) is limited. Here we report the incidence, impact on survival, and risk factors for SRE in patients with mNSCLC treated with first-line pembrolizumab monotherapy or pembrolizumab plus chemotherapy. We conducted a retrospective study of patients with mNSCLC treated with first-line pembrolizumab or pembrolizumab plus chemotherapy at our institution from 2017-2020. The associations between SRE and categorical variables were studied using Fisher’s exact test and with continuous variables using the Kruskal-Wallis test. Kaplan-Meier plots were used to visualize survival curves. The association between baseline BM and OS was examined using a Cox proportional hazard model. OS was calculated from date of ICI initiation to death from any cause or last follow-up. We identified a cohort of 202 patients: 93 (46%) treated with pembrolizumab and 109 (54%) treated with pembrolizumab plus chemotherapy; 39 (19%) had squamous histology and 163 (81%) had nonsquamous histology; median age 62.7; median OS 33.7 months (95% CI: 17.2 – NR). In our cohort, 87 (43%) patients had BM at time of ICI initiation and 47 (23%) developed SRE after ICI initiation. Patients who developed SRE were more likely to have baseline BM than those without SRE (91.5% vs 28.4%, p<0.001). Development of BM during treatment with ICI and performance status were also significantly associated with SRE (p<0.001 and p=0.006, respectively). Patients with BM at time of ICI, or development of new or progression of existing BM while on ICI, had shorter survival than those without (Figure 1a and Figure 1b, respectively). In multivariate survival analysis, the hazard of death for patients with baseline BM was 2.85 times those without (HR=2.85, 95% CI: 1.53, 5.29, p-value=0.0009) after controlling for age, BMI, performance status, histology, PD-L1 expression, smoking, and SRE. The use of bone-modifying agents (BMA) was not associated with OS, osseous progression, or risk of SRE. The presence of BM at time of ICI was associated with shorter survival after controlling for multiple clinical characteristics. These patients represent a high-risk cohort for worse outcomes when treated with ICI alone or in combination with chemotherapy. In our cohort BMA were not associated with increased OS or decreased risk of osseous progression or SRE.

Abstract PS9-30: The efficacy of a comprehensive bone health program in maintaining bone mineral density in postmenopausal women with early-stage breast cancer treated with endocrine therapy

Abstract Introduction: Given the recent advances in early detection, improving access to care and the introduction of more effective anti-cancer medications including endocrine therapy, targeted and immunotherapy, more women with breast cancer survive their disease. Majority of patients with breast cancer express hormone receptors (estrogen and or progesterone receptors) on cancer cells. Aromatase inhibitors (AI) are the gold standard treatment of hormone-sensitive postmenopausal women with breast cancer. Several studies had documented the accelerated bone loss associated with AI. The use of bone modifying agents like bisphosphonates and denosumab had resulted in significant improvement in bone mineral density among females treated with AI. In this paper, we study the efficacy of implementing a comprehensive program on bone health for such patients. Patients and Methods: Postmenopausal women with hormone-sensitive early-stage breast cancer treated with endocrine therapy (ET) were included. A comprehensive bone health program was implemented. The program includes extensive counselling by medical oncologist, calcium and vitamin-D supplements, increase milk intake and exercise. Patients with baseline lumbar spine or total hip T-scores ≥ -2 were given short intravenous bisphosphonate infusion every 6 months. Patients with osteoporosis are referred to and followed in a specially designed “osteoporosis clinic”. Results: Between 2013 and 2019, a total of 210 patients fulfilled the eligibility criteria and were enrolled. All were female, median (range) age 67 (43-86) years. All patients had a pathologically confirmed diagnosis of breast cancer, treated and followed up at our institution. High risk patients (n=103, 49.0%) were treated with 6-8 cycles of chemotherapy, including anthracyclines and taxanes. Following the completion of chemotherapy, all patients were treated with endocrine therapy. Patients with low-risk disease (n=107, 51.0%) were treated with upfront endocrine therapy-alone. Aromatase inhibitors, letrozole or anastrozole, were the endocrine therapy of choice in all patients. At baseline, and prior to start of AI, the median T-scores at the hip and lumber spines were -1.0 (range: -3.6, 1.9) and -1.4 (range: -3.9, 2.6), respectively. Osteoporosis was documented in 38 (18.1%) patients while 101 (48.1%) others had osteopenia; none were on any treatment or even aware of their BMD. 46 (25.3%) patients had vitamin-D deficiency while 74 (40.7%) others had vitamin-D insufficiency and none were on prior active replacement therapy or even aware of this problem. Following at least 12-months of endocrine therapy, 32 (84.2%) of patients with osteoporosis and 69 (68.3%) of those with osteopenia had a stable or higher BMD. Thus, the number of patients with osteoporosis declined to 27, 12.9% of the total cohort. On the other hand, 41 (57.7%) of those with normal baseline BMD had a drop in their follow up BMD. Vertebral fractures, presented with back pain and documented by imaging studies, were reported in 3 (11.1%) patients with osteoporosis compared to none in patients with normal BMD, p=0.021. Rib fracture and hip fracture were reported in one patient each and both had normal BMD before and after AI therapy. Conclusions: Postmenopausal women with breast cancer are at risk of osteopenia and osteoporosis. Such risk increases significantly with the use of AI. However, early interventions with modifiable risk factors, Vitamin-D supplements and use of bone-modifying agents can lower this risk. Citation Format: Razan Mansour, Ula Al-Rasheed, Akram Al-Ibraheem, Shereen Abu Jaradeh, Rashid Abdel-Razeq, Rayan Bater, Noor Mashahdani, Shrouq Tbayshat, Hikmat Abdel-Razeq. The efficacy of a comprehensive bone health program in maintaining bone mineral density in postmenopausal women with early-stage breast cancer treated with endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-30.

Real-world practice patterns and attitudes towards de-escalation of bone-modifying agents in patients with bone metastases from breast and prostate cancer: A physician survey

BackgroundThere remain questions around the optimal use of bone-modifying agents (BMAs) in patients with bone metastases from breast and castration-resistant prostate cancer (CRPC). A physician survey was performed to identify current practices, as well as perceptions around long-term BMA use, BMA de-escalation, and further BMA de-escalation after 2 years of use. MethodsCanadian oncologists treating breast cancer or CRPC were surveyed via an anonymized online survey. The survey collected physician demographics, current practice patterns, perception on risk of symptomatic skeletal events (SSE) and BMA-associated toxicities, and attitudes towards further de-escalation of BMAs after 2 years of treatment. ResultsA total of 334 physicians in Canada were contacted, of which 295 were eligible on initial screening, and 65 completed the survey (response rate 22%): 35 treated breast cancer, 25 treated prostate cancer and 5 treated both. The most common BMA regimens in patients with no limitation in drug coverage were denosumab q4wks for 3–4 months followed by a de-escalation to q12wks (breast cancer) and denosumab q4wks (prostate cancer). In patients with provincial health coverage only the common choices were zoledronate q4wks for 3–4 months followed by de-escalation to q12wks (breast cancer) and denosumab q4wks (prostate cancer). There was equipoise regarding the benefit of continuing BMA beyond 2 years and interest in further trials of de-escalation of BMA in both breast and prostate cancer. The most favored alternative primary study endpoints to SSE were BMA toxicity (67.2%), pain (46.9%), and physical function (48.4%). ConclusionDespite their extensive use and costs, questions around optimal use of BMAs still exist. Practice varies according to patient insurance coverage. However, most physicians are de-escalating BMAs. There is interest amongst clinicians in performing trials of de-escalation, especially after 2 years of treatment.

506 Poster - Effect of the COVID-19 pandemic on use of bone-modifying agents for metastatic breast cancer in a UK Oncology centre

Background: Bone-modifying agents (BMAs) prevent skeletal-related events (SREs) in breast cancer patients with bone metastases. Our centre uses mainly zoledronic acid (ZA). Denosumab is permitted, due to its high cost, only with a documented indication such as renal failure. ASCO/CCO guidelines have responded to Phase 3 trial evidence showing non-inferiority of 12-weekly ZA compared to 3 or 4-weekly, which may reduce adverse events (AEs) and cost. We report on patterns of prescription in our centre and how it has changed due to COVID-19. Materials and methods: Data was retrospectively collected on patients who received BMAs in two separate three-month periods (Oct-Dec 2019 and Apr-Jun 2020, total n = 389) including choice of BMA, frequency of administration, concurrent systemic therapy, and incidence of SREs and AEs. We searched the electronic prescribing record, outpatient letters, radiotherapy record and blood tests for each patient. Results: Of the patients receiving BMAs in period one, 88% were on ZA and 13% on denosumab. Of those on denosumab, the majority (79%) had a documented indication, of which the most common (68%) was poor renal function. Mean total duration of BMA therapy was 22 months, during which 26% received radiotherapy to the bone. We found 3 cases of osteonecrosis of the jaw (ONJ), no osteonecrosis of the auditory canal (ANAC), and no atypical femoral fractures (AFF) out of the patients still receiving BMAs in period one. 32% experienced hypocalcaemia, defined as any reading below the laboratory reference range since starting BMA therapy. In period two, 11% fewer patients received BMAs. There was a large variation in intervals prescribed within period one (Table 1) and a marked shift thereafter. The percentage of patients on 12-weekly treatment rose from 45% to 66%. The change resulted in a saving of approximately £1300 in medication cost and 60 hours of nursing time. If all patients were on 12-weekly dosing, this could save approximately a further £2400 and 120 nursing hours per year. Hypocalcaemia occurred in 8.5% of patients during period one and 7.0% during period two.Tabled 1Period one N = 205Period two N = 183ZA88%84%Denosumab13%16%4-weekly24%6%6-weekly13%10%8-weekly17%18%12-weekly45%66%Other frequency2%0%Concurrent chemotherapy30%34% Open table in a new tab Conclusions: Despite strong evidence supporting use of 12 weekly ZA, local practice was slow to change. During COVID-19 it became necessary to minimise exposure of patients to hospital. This resulted in a rapid shift in practice; leading to reduced treatment burden, less hypocalcaemia, liberation of nursing time and cost saving in the COVID-19 period and beyond. No conflict of interest.

Prognosis and safety of radium-223 with concurrent abiraterone acetate or enzalutamide use for metastatic castration-resistant prostate cancer: Real-world data of Japanese patients.

ObjectivesTo evaluate the real‐world data on the efficacy and safety of a combination therapy with radium‐223 (Ra‐223) and second‐generation androgen‐receptor targeting agents (ARTAs), including abiraterone acetate (ABI) and enzalutamide (ENZ), among Japanese patients with bone metastatic castration‐resistant prostate cancer (CRPC).Patients and methodsWe retrospectively reviewed 79 patients with bone metastatic CRPC who were treated with Ra‐223. The number of patients with concurrent ARTA use was 24:17 receiving ABI and 7 receiving ENZ. We evaluated the overall survival (OS) according to ARTA use and compared the survival of patients treated with Ra‐223 with or without ARTA using multivariate analysis.ResultsThe median survival in the entire cohort was 23.5 months. The patients receiving Ra‐223 combined with ARTA showed a tendency of better OS than patients treated with Ra‐223 alone, although no significant difference was observed (median OS, 26.5 vs 23.5 months; P = .115). A multivariate analysis showed that the extent of disease on bone scan (EOD) scores and pain at baseline were significant predictors of OS. The concurrent use of bone‐modifying agents (BMAs) was not significant for favorable OS (P = .050). However, the concurrent use of second‐generation ARTA was not a significant factor for OS. Regarding safety, a bone fracture occurred in only one (4.2%) of 24 patients treated with combined Ra‐223 and ARTA therapy.ConclusionOur real‐world data analysis suggested that Ra‐223 combined with a second‐generation ARTA is well tolerated in Japanese patients. The EOD score and pain at baseline are significant prognostic factors for OS, but the concurrent use of second‐generation ARTA has no influence on OS among men treated with Ra‐223. The concurrent use of BMA yields a marginally favorable OS.

Role of bone-modifying agents in advanced cancer.

Bone lesions from metastatic solid tumors and multiple myeloma (MM) represent an important source of morbidity in patients with incurable malignancies. Dysregulation of osteoclast and osteoblast activity caused by tumor cells in the bone microenvironment weakens the structural integrity of bone and predisposes to skeletal-related events (SREs), which can include severe bone pain, pathologic fracture, spinal cord compression and hypercalcemia. In order to reduce the risk of these complications, the supportive treatment of patients with bone lesions from advanced cancer typically includes the use of bone-modifying agents (BMAs), specifically bisphosphonates and denosumab. The choice of specific agent, dosing schedule and duration of therapy should be individualized by taking into account disease characteristics, medication side-effect profiles and patient preferences.

Use of Bone-Modifying Agents Among Medicare Beneficiaries With Multiple Myeloma

Use of Bone-Modifying Agents Among Medicare Beneficiaries With Multiple Myeloma

Use of bone‐modifying agents and clinical outcomes in older adults with multiple myeloma

BackgroundGuidelines recommend bone‐modifying agents (BMAs) for all patients initiating treatment for myeloma. We examined adherence to this recommendation, and BMA effectiveness in the era of bortezomib/lenalidomide‐based therapy among Medicare beneficiaries.MethodsFrom the linked Surveillance, Epidemiology, and End Results‐Medicare registry, we selected beneficiaries receiving anti‐myeloma chemotherapy in 2007‐2013. We matched BMA recipients (within 90 days of first chemotherapy) to nonrecipients using a propensity score, balancing patient‐, disease‐, and therapy‐related confounders. Cumulative incidence of skeletal‐related events (SREs) and overall survival (OS) was compared in proportional hazard models accounting for competing risks and immortal‐time bias.ResultsAmong 4611 patients with median age of 76 years, 51% received BMA. Bone‐modifying agents use remained steady over time (P = .87) and was significantly less frequent for patients who were older, with comorbidities, without prior SRE, and those treated without bortezomib or lenalidomide. In a propensity score‐matched cohort, BMA recipients experienced a lower incidence of SRE (11.0% vs 14.6% at 3 years; subhazard ratio, 0.73; 95% CI, 0.60‐0.89) and better OS (53.3% vs 47.8% at 3 years; hazard ratio, 0.86; 95% CI, 0.77‐0.95). The results were consistent in the subgroup (76%) treated with bortezomib and/or immunomodulatory drugs (IMiDs). The incidence of osteonecrosis of the jaw (ONJ) was 3.2% at 3 years.ConclusionsIn this observational study, the observed benefits of early BMA administration among patients treated with contemporary anti‐myeloma regimens were similar to historical clinical trials. Frequent omission of BMA highlights a remediable deficiency in the quality of supportive care, and suggests that timely administration may be a useful indicator of quality care in myeloma.