Osteonecrosis of the jaw (ONJ) in radium 223 (Ra223)-treated metastatic castration-resistant prostate cancer (mCRPC) patients (pts) with exposure to zoledronic acid and/or denosumab.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5575-5575
Author(s):  
Yen Thi Kim Hong Cao ◽  
Janson Trieu ◽  
Vanessa Rojas ◽  
Michael Elias ◽  
Michael J. Anderson ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Metastases ◽  
Data Entry ◽  
Sequential Therapy ◽  
Median Number ◽  
Osteonecrosis Of The Jaw ◽  
Sequential Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Sequential Group

5575 Background: Bone health agents (BHA) including denosumab, a monoclonal antibody, and Zoledronic acid (ZA), a bisphosphonate, are recommended for men with CRPC and bone metastases to prevent skeletal-related complications. ONJ occurs in about 5% of patients (pts) on BHA. The incidence of ONJ in pts treated with Ra223 and BHA remains unknown, particularly in those who receive sequential treatment of BHAs. Here we describe the rate of ONJ in a real-world setting in mCRPC pts treated with Ra223 in 3 groups: 1) denosumab alone, 2) ZA alone, and 3) sequential ZA /denosumab or vice versa. Methods: A retrospective analysis of a cohort of mCRPC pts with bone metastases who received Ra223. Follow-up was until date of death or last data entry. Chart inclusion criteria included patients who received Ra223 between November 2010 to August 2018 with documentations of data points. Results: A total of 177 pts received Ra223 between 11/2010 and 8/2018. Median age 73 at 1st Ra223 (range 40-93); Median PSA 15.8- at 1st Ra223 (range 0.1-1952); Demographics-AA-10, C-130, Asian-9, unspecified-28; Median Alk Phos 95 at 1st Ra233 (range 25-1515). 93 % (164/177) received BHA. Of the 164 who received BHA, 45% (73/164) received denosumab only, 37% (61/164) received ZA only, and 18% (30/164) received sequential treatment. ONJ developed in 9.7% (16/164) of all patients on BHA. Denosumab alone caused ONJ in 7 of 73 pts (9.6%). ZA alone caused ONJ in 6 of 61 pts (9.8%). ONJ occurred in 3 of 30 pts (10%) in the sequential group. The median number of doses of BHA before development of ONJ was 10 with denosumab, 20 with ZA, and 19.5 (denosumab) and 22 (ZA) in the sequential group. Conclusions: In patients treated with Ra223 and a BHA, the rate of ONJ is 9.7%. The rate of ONJ was similar in groups treated with denosumab alone, ZA alone, and sequential treatment of ZA and denosumab However, ONJ developed more quickly in patients on denosumab. We conclude that the risk of ONJ is increased in patients treated with Ra223 and BHA. ZA or sequential therapy appears to delay time to onset of ONJ compared to denosumab. Clinicians should be mindful of the toxic synergy between Ra223 and BHA. ZA may be the preferred BHA partner with Ra223.

Randomized trial of marker-directed versus standard schedule zoledronic acid for bone metastases from breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 511-511 ◽  
Author(s):  
Robert Edward Coleman ◽  
Jonathan Wright ◽  
Stephen Houston ◽  
Rajiv Agrawal ◽  
Om Pra-Kash Purohit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Type I Collagen ◽  
Treatment Strategies ◽  
Median Number ◽  
Osteonecrosis Of The Jaw ◽  
Treatment Schedule ◽  
Type I ◽  
Skeletal Related Events

511 Background: Zoledronic acid (ZOL) reduces skeletal morbidity associated with metastatic bone disease by 30-50%. Current recommendations are for indefinite administration of intravenous 3-4 weekly (w) ZOL 4mg. Over recent years it has become clear that the risk of skeletal morbidity is related to the rate of bone resorption. We have compared a marker directed schedule of ZOL (M-ZOL), using measurements of urinary n-telopeptide of type I collagen (NTX), to a standard treatment schedule (S-ZOL) in patients with bone metastases from breast cancer. Methods: The primary endpoint was skeletal related events (SRE). A non-inferiority study was designed with 80% power and (one-sided) 5% alpha to demonstrate that M-ZOL retained 67% of the efficacy of S-ZOL. This required 1500 patients, assuming a SRE rate of 0.7/year. Following minimisation for known prognostic factors, patients were randomised to receive S-ZOL 3-4 w or M-ZOL (15-16w; 8-9 w or 3-4w if NTX levels were <50, 50-100, >100 nmol/mmol creatinine respectively), with the schedule adjusted according to NTX measured every 16 weeks. The study duration was 24 months. Results: Due to lower than expected recruitment, the study closed in 2009 following recruitment of 289 patients. 90% of patients had received >4 cycles of ZOL or pamidronate prior to randomisation. The median number of ZOL infusions administered to S-ZOL patients was >2x that received on M-ZOL. 46 (32%) S-ZOL and 55 (38%) M-ZOL patients experienced an SRE. The numbers of SRE were 94 and 138 in the S-ZOL and M-ZOL arms, with the excess in SRE being largely due to more patients on M-ZOL experiencing ≥2 SRE. Multivariate analysis adjusting for key minimisation factors and baseline NTX for all SRE showed a hazard ratio for M-ZOL vs. S-ZOL of 1.41 (90%CI 0.98-2.02, p=.12). NTX levels were significantly higher at all time points in the M-ZOL treated patients. Osteonecrosis of the jaw was uncommon with 3 cases with S-ZOL and 1 with M-ZOL. Conclusions: The study is underpowered to demonstrate non-inferiority in SRE outcome between the treatment strategies. However, the results suggest that the adjustment of ZOL schedule based on NTX values alone may represent sub-optimal management.

scholarly journals Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

2021 ◽  
Author(s):  
Hiroaki Ikesue ◽  
Moe Mouri ◽  
Hideaki Tomita ◽  
Masaki Hirabatake ◽  
Mai Ikemura ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Metastases ◽  
Tooth Extraction ◽  
Proportional Hazards ◽  
Osteonecrosis Of The Jaw ◽  
Cox Proportional Hazards ◽  
Patients With Cancer ◽  
Proportional Hazards Regression ◽  
Before And After ◽  
Denosumab Treatment

Abstract Purpose This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

Bone modifying agents in veterans with castration-resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6582-6582
Author(s):  
Jordan Bauman ◽  
Kyle Kumbier ◽  
Jennifer A. Burns ◽  
Jordan Sparks ◽  
Phoebe A. Tsao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Specific Antigen ◽  
Veterans Health ◽  
Health Administration ◽  
Castration Resistant Prostate Cancer ◽  
National Guidelines ◽  
Castration Resistant ◽  
Unit Increase

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.

scholarly journals Re‐treatment with radium‐223: 2‐year follow‐up from an international, open‐label, phase 1/2 study in patients with castration‐resistant prostate cancer and bone metastases

The Prostate ◽  
2019 ◽  
Vol 79 (14) ◽  
pp. 1683-1691 ◽  
Author(s):  
Oliver Sartor ◽  
Daniel Heinrich ◽  
Neil Mariados ◽  
Maria José Méndez Vidal ◽  
Daniel Keizman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Phase 1 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Radium 223 ◽  
Open Label Phase
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