Denosumab versus bisphosphonates in patients with advanced cancers-related bone metastasis: systematic review and meta-analysis of randomized controlled trials

Menshawy, Amr; Mattar, Omar Mohamed; Abdulkarim, Ali; Kasem, Shiref A.; Nasreldin, Noha; Menshawy, Esraa; Mohammed, Shafiu; Abdel-Maboud, Mohamed; Gadelkarim, Mohamed; Ashal, Gehad Gamal E. l.; Elgebaly, Ahmed

doi:10.1007/s00520-018-4060-1

Cited by 50 publications

(45 citation statements)

References 34 publications

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“…Experience in the use of BMAs comes from studies in advanced breast and prostate cancers. Indeed, in a recent meta-analysis of 6 large randomised-controlled trials, including a variety of solid tumours, both bisphosphonates and denosumab prolong time to SREs, with overall superiority in the latter [16]. Clinical trials clarifying the role of BMAs as primary prevention of SREs in patients with BMs specifically from NEN are therefore required.…”

Section: Discussionmentioning

confidence: 99%

Identification of Areas for Improvement in the Management of Bone Metastases in Patients with Neuroendocrine Neoplasms

Lim¹,

Raja²,

D'Arienzo³

et al. 2019

Neuroendocrinology

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Background: There is no global consensus on the optimal management of bone metastases (BMs) in neuroendocrine neoplasms (NENs). Objectives: To review current management and outcomes of patients with BMs in NENs, in order to identify areas for improvement. Methods: A retrospective study of all patients with NENs, except Grade 3 lung NENs (April 2002 to March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 23.0/STATA v12. Results: Of 1,212 patients, 85 (7%) had BMs; median age 58 years. The majority had a gastro-entero-pancreatic primary (49%, n = 42) followed by lung (25%, n = 21), unknown primary (20%, n = 17), and "others" (6%, n = 5). Two-thirds (n = 57) had G1-2 neuroendocrine tumours, and 41% (n = 35) had functional tumours. Overall, 28% (n = 24) presented with synchronous BMs at first NEN diagnosis, and 55% (n = 47) developed BMs at the same time as other distant metastases. For the subpopulation of patients in whom BMs developed metachronously to other distant metastases (45%, n = 38), median time to development of BMs was 14.0 months. BMs were "widespread" in 61% (n = 52). Although only 22% (n = 19) reported symptoms at initial diagnosis of BMs, most (78%) developed symptoms at some time during the follow-up period (pain/hypercalcaemia 64%, skeletal-related events 20%). BMs were mainly managed with analgesia (44%, n = 37). Radiotherapy and bisphosphonates were used in 34% (n = 29) and 22% (n = 19) respectively. Surgery was rarely performed (2%, n = 2). Median OS from identification of BMs was 31.0, and 18.9 months from development of BMs-related symptoms. Conclusions: In this cohort study, most patients with BMs developed symptoms. The utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patients' quality of life and survival outcomes.

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Section: Discussionmentioning

confidence: 99%

Identification of Areas for Improvement in the Management of Bone Metastases in Patients with Neuroendocrine Neoplasms

Lim¹,

Raja²,

D'Arienzo³

et al. 2019

Neuroendocrinology

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“… 39 This is not something that can be determined from large pivotal trials because the life expectancy of patients with metastatic breast cancer involving the bone may approach or exceed the median length of follow-up in these studies. 40 – 42 For some women with skeletal metastases from breast cancer, life span can be relatively long, exceeding 5 years in 12.5% of the cases; 4 thus, these women may be at risk of experiencing a bone complication for several years after their diagnosis of bone metastases. Along with the potential long-term benefits of the drugs, clinicians must also consider the risk of adverse events, including osteonecrosis of the jaw and hypocalcemia.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent meta-analysis, denosumab was associated with increased risk of grade 3 or 4 hypocalcemia (relative risk: 1.99; 95% CI: 1.11, 3.54) in comparison to intravenous bisphosphonates, due to denosumab’s powerful antiresorptive effect and reduced risk of renal impairment or toxicity (relative risk: 0.75; 95% CI: 0.61, 0.91) in comparison to intravenous bisphosphonates. 40 The rates of osteonecrosis of the jaw can be higher for individuals treated with antiresorptives for longer durations. 41 Health care providers should discuss the risks and benefits of BMA therapy with the patients with breast cancer who have metastatic bone disease.…”

Section: Discussionmentioning

confidence: 99%

Use of bone-modifying agents among breast cancer patients with bone metastasis: evidence from oncology practices in the US

McGrath¹,

Overman²,

Reams³

et al. 2018

CLEP

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PurposeBone-modifying agents (BMAs) are recommended for women with bone metastasis from breast cancer to prevent skeletal-related events. We examined the usage patterns and identified the factors associated with the use of BMAs (denosumab and intravenous bisphosphonates) among women in the US.Patients and methodsElectronic health records from oncology clinics were used to identify women diagnosed with bone metastasis from breast cancer between 2013 and 2014. Patients were excluded if they had recently used a BMA or had concurrent cancer at an additional primary site. The incidence of BMA initiation, interruption, and reinitiation were estimated using competing risk regression models. A generalized linear model was used to estimate risk factors for treatment initiation and interruption.ResultsThere were 589 women diagnosed with bone metastasis from breast cancer. By 1 year, 68% of these patients (95% CI: 64%, 71%) had initiated treatment with a BMA. Denosumab and zoledronic acid were the most commonly used agents, whereas pamidronate was used infrequently. Young women were more likely to initiate a BMA than older women (adjusted risk difference: 6.4 [95% CI: 1.5, 10.9]). Of the 412 patients who initiated a BMA, 46% (95% CI: 41%, 51%) experienced an interruption within 1 year. Seventy-four percent (95% CI: 68%, 79%) of patients who interrupted their treatment had reinitiated therapy within 1 year of interruption.ConclusionThe majority of women diagnosed with bone metastasis from breast cancer initiate a BMA within 1 year of diagnosis, but a large proportion, particularly among the elderly, do not use these therapies.

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“…It should be clear to all oncologists that osteoprotective therapy and related supplementation of calcium and vitamin D is indispensable in patients with bone metastases to avoid skeletal-related complications and to postpone their occurrence during the course of the disease [22]. As a general conclusion, guidelines must be combined with an effective concept and strategy of implementation.…”

Section: Discussionmentioning

confidence: 99%

Guideline adherence in bone-targeted treatment of cancer patients with bone metastases in Germany

Diel

Ohlmann

Holtmann³

et al. 2019

Support Care Cancer

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Purpose To assess adherence to the current European Society for Medical Oncology (ESMO) clinical practice guideline on bone health in cancer patients and the German guidelines for lung, breast, and prostate cancer among German oncologists in hospitals and office-based physicians and to identify predictors of guideline compliance to assess the needs for dedicated training. Methods This was a retrospective sample analysis representing hospitals and office-based physicians in Germany in 2016. Records from lung, breast, and prostate cancer patients who had received a diagnosis of bone metastasis between April 1, 2015, and March 31, 2016, were included. Oncologists at participating centers answered a self-assessment survey on aspects related to their professional life, including guideline adherence and years of clinical experience in medical oncology. Guideline adherence rates were assessed from patient records. Treatment variables and survey data were used to identify predictors of guideline compliance in a Classification and Regression Tree (CART) analysis. Results Disregarding recommendations for supplementation of calcium and vitamin D, guideline adherence among physicians treating lung, breast, or prostate cancer patients was 62%, 92%, and 83%, respectively. Compliance was 15%, 42%, and 40% if recommendations for dietary supplements were taken into account. Identified predictors of guideline compliance included treatment setting, medical specialty, years of professional experience, and frequency of quality circle attendance. Conclusions Compliance with the ESMO and the German guidelines in cancer patients varies between medical specialties. In particular, patients with lung cancer and bone metastases often do not receive the recommended osteoprotective treatment and required supplementation. Discrepancies between guideline recommendations and common practice should be addressed with dedicated training.

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Denosumab versus bisphosphonates in patients with advanced cancers-related bone metastasis: systematic review and meta-analysis of randomized controlled trials

Cited by 50 publications

References 34 publications

Identification of Areas for Improvement in the Management of Bone Metastases in Patients with Neuroendocrine Neoplasms

Identification of Areas for Improvement in the Management of Bone Metastases in Patients with Neuroendocrine Neoplasms

Use of bone-modifying agents among breast cancer patients with bone metastasis: evidence from oncology practices in the US

Guideline adherence in bone-targeted treatment of cancer patients with bone metastases in Germany

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