Bone modifying agents for patients with bone metastases from breast cancer managed in routine practice setting: Treatment patterns and outcome

2019 ◽  
Vol 26 (4) ◽  
pp. 906-911
Author(s):  
Jamal Zekri ◽  
Kamel Farag ◽  
Osama Yousof ◽  
Yazeed Zabani ◽  
Wael Mohamed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Treatment Patterns ◽  
Routine Practice ◽  
Related Event ◽  
Modifying Agent ◽  
Skeletal Related Events ◽  
Skeletal Related Event

Introduction Bone metastases are common in patients with breast cancer and can lead to pain and skeletal-related events. Bone modifying agents are licensed to be used for these patients. We report the treatment patterns and outcome of zoledronic acid and denosumab in routine practice. Methodology Women with bone metastases from breast cancer who have started denosumab or zoledronic acid between 2011 and 2016 were eligible. Those with history of bone modifying agent use prior to diagnosis of bone metastases or with switching treatment between zoledronic acid and denosumab were excluded. Details of patients, tumors, bone modifying agent treatment, selected bone modifying agent toxicity, time to skeletal-related event development, and overall survival were collected retrospectively. Results In total, 163 women were eligible and included in this analysis. Number of skeletal-related events prior to starting bone modifying agents was 0, 1, 2, and 3 in 91 (55.8%), 53 (32.5%), 13 (8%), and 6 (3.7%), respectively. Zoledronic acid was started for 107 (65.6%) and denosumab for 56 (34.4%) patients. The proportion of patients receiving denosumab increased from 23.1 to 54.3% in years 2011 and 2016, respectively. Dose delay, reduction, and discontinuation due to toxicity were reported more frequently in patients receiving zoledronic acid. Denosumab delayed time to first on-treatment skeletal-related event compared with zoledronic acid (hazard ratio, 0.64; 95% CI, 0.41–0.98; log rank P = 0.044). There was no significant difference in median survival (zoledronic acid: 62 and denosumab: 58 months; log rank P = 0.956). Conclusion Denosumab is superior to zoledronic acid in reducing risk of skeletal-related events and in tolerance profile. However, overall survival is similar with both treatments. Our findings mirror those reported in scrutinized environment of landmark clinical trials.

scholarly journals A phase II study of palliative radiotherapy combined with zoledronic acid hydrate for metastatic bone tumour from renal cell carcinoma

2020 ◽  
Vol 51 (1) ◽  
pp. 100-105
Author(s):  
Hideyuki Harada ◽  
Naoto Shikama ◽  
Hitoshi Wada ◽  
Nobue Uchida ◽  
Miwako Nozaki ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Palliative Radiotherapy ◽  
Level Increase ◽  
Skeletal Related Events ◽  
Acid Hydrate ◽  
Skeletal Related Event

Abstract Purpose Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. Methods Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. Results Twenty-seven patients were included in the study. The median age was 65 (range, 50–84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0–34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2–89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. Conclusion Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.

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.

Safety and efficacy of bone-modifying agents among multiple myeloma patients: A retrospective cohort study

2021 ◽  
pp. 107815522199603
Author(s):  
Christina Billias ◽  
Megan Langer ◽  
Sorana Ursu ◽  
Rebecca Schorr
Keyword(s):  
Multiple Myeloma ◽  
Cohort Study ◽  
Zoledronic Acid ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Osteonecrosis Of The Jaw ◽  
Safety And Efficacy ◽  
Modifying Agent ◽  
Skeletal Related Events ◽  
Agent Group

Objective To determine the incidence of skeletal-related events among multiple myeloma patients who received chemotherapy without a bone-modifying agent (zoledronic acid and denosumab) versus those who received chemotherapy with a bone-modifying agent. The secondary objective was to determine the incidence of skeletal-related events in patients without any prior history of skeletal-related events and who were treated with zoledronic acid every four weeks versus those who received zoledronic acid at an extended interval of every twelve weeks. Additional secondary objectives included the incidence of nephrotoxicity, hypocalcemia and osteonecrosis of the jaw in all patients. Methods This institutional review board-approved, retrospective cohort study included patients 18 to 89 years old with a diagnosis of multiple myeloma, who were being treated with chemotherapy between July 1, 2016 and October 31, 2019. Safety and efficacy were assessed through analysis of pertinent data collected: patient demographics, baseline skeletal-related events, development of new skeletal-related events, number and type of bone-modifying agent doses administered, and drug-related toxicities such as nephrotoxicity, hypocalcemia, and osteonecrosis of the jaw. Results A total of 73 patients were included. New skeletal-related events occurred in 12 patients (27%) in the chemotherapy without a bone-modifying agent group and in 5 patients (17%) in the chemotherapy with a bone-modifying agent group (OR = 0.56, 95% CI [0.172–1.8]; P = 0.32). The incidence of skeletal-related events was similar among patients receiving zoledronic acid every four weeks versus every twelve weeks in patients without a prior skeletal-related event (N = 0 vs. N = 2 respectively; P = 0.47). There were no statistically significant differences observed in each of the three secondary safety endpoints: incidence of hypocalcemia, nephrotoxicity and osteonecrosis of the jaw. Conclusion Multiple myeloma patients receiving chemotherapy without a bone-modifying agent had higher rates of skeletal-related events compared to those being treated with chemotherapy and a bonemodifying agent. Our results highlight the benefit of utilizing bonemodifying agents for the prevention of skeletal-related events in all multiple myeloma patients being treated with chemotherapy.

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