Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials

Galvano, Antonio; Scaturro, Dalila; Badalamenti, Giuseppe; Incorvaia, Lorena; Rizzo, Sérgio; Castellana, Luisa; Cusenza, Stefania; Cutaia, Sofia; Santini, Daniele; Guadagni, Fiorella; Roselli, Mario; Gori, Stefania; Latteri, M; Bazan, Viviana; Giulia, Letizia Mauro

doi:10.1016/j.jbo.2019.100252

Cited by 25 publications

(21 citation statements)

References 33 publications

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“…Of the 18 selected research papers, there were seven RCTs using denosumab in breast cancer and prostate cancer [9,[15][16][17][18][19][20]. Three of these RCTs evaluated the role of denosumab in breast cancer [16,17,18], while one evaluated the role of denosumab in prostate cancer [15].…”

Section: Resultsmentioning

confidence: 99%

“…Three of these RCTs evaluated the role of denosumab in breast cancer [16,17,18], while one evaluated the role of denosumab in prostate cancer [15]. There were two systematic reviews and meta-analyses that compared the role of denosumab with bisphosphonates in both prostate cancer and breast cancer [9,20]. Both meta-analyses included studies published beyond the last five years in this population.…”

Section: Resultsmentioning

confidence: 99%

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Comparing the Efficacy and Safety of Denosumab with Bisphosphonates in Increasing Bone Mineral Density in Patients with Prostate Cancer and Breast Cancer on Antihormonal Treatment

Razaq¹,

Khan

Hassan

et al. 2019

Cureus

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Osteoporosis is a common condition prevalent in both sexes that can be primary and secondary. Secondary osteoporosis may occur in cancer patients undergoing antihormonal treatment, leading to an increased risk of fractures. Androgen deprivation therapy (ADT) in patients with prostate cancer and aromatase inhibitors (AI) in patients with breast cancer can drastically increase the risk of osteoporosis. Bisphosphonates are one of the key medications in managing these patients and are widely prescribed. A monoclonal antibody called denosumab, which is a relatively new treatment option, is also used in this population group. To conduct a detailed comparison of these groups, we performed a thorough literature search using Pubmed and Google Scholar to extract data in the form of research papers/clinical trials. A total of 18 research papers were extracted using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and other inclusion and exclusion criteria. Seven of these papers were based on randomized controlled trials (RCTs) comparing denosumab with either placebo or bisphosphonates in patients with breast cancer and prostate cancer. Two metaanalyses comparing the safety and efficacy of both these drugs in this population group were also included. Denosumab was found to significantly increase bone mineral density (BMD) for up to two years and showed better results than bisphosphonates, while both had a comparable safety profile. More trials should be conducted in patients with prostate cancer or breast cancer on ADT or AI therapy, respectively, for longer durations to assess the long-term safety of these drugs in this population.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Comparing the Efficacy and Safety of Denosumab with Bisphosphonates in Increasing Bone Mineral Density in Patients with Prostate Cancer and Breast Cancer on Antihormonal Treatment

Razaq¹,

Khan

Hassan

et al. 2019

Cureus

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“…Recently, a new drug blocking RANK/RANKL/ OPG pathway exerts bone control with the prevention of bone resorption and destruction: denosumab, a fully human monoclonal antibody (anti-RANKL), authorized for the treatment/prevention of SREs in bone metastases from MM, breast, prostate cancer and Ewing Sarcoma. Better than zoledronic acid, denosumab decreases the number of SREs, delays SREs onset, reduces bone pain and prevents immune system preservation by the differentiation and survival of B cell, T cell and DCs (both in bone niche and blood) [60,65]. Initial preclinical data evidenced a possible role in systemic tumor control with better progression and overall survival, but strongly results are warranted.…”

Section: Bone Targeted Drugs Have a Role In Anticancer Systemic Theramentioning

confidence: 99%

“…Current clinical studies are evaluating to a greater extent the effect of denosumab on survival and other biomarkers. Multiple myeloma [48,49] Breast cancer [48,49,50] Lung cancer [64] Renal cell carcinoma [53] Prostate cancer [49] Denosumab Multiple myeloma [58] Breast cancer [59,60] Prostate cancer [59,60,62,63] Hepatocellular carcinoma [55] Ewing Sarcoma [65] ANTICANCER DRUGS PLAY EFFECT…”

Section: Bone Targeted Drugs Have a Role In Anticancer Systemic Theramentioning

confidence: 99%

Immune system and bone microenvironment: rationale for targeted cancer therapies

et al. 2020

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Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator of NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.

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“…Initial data evidenced a possible role in systemic tumor control with better progression and overall survival. In addition, in this case the systemic anti-cancer effect seems due to a better immune system regulation, T-cell activation and immunogenic chemokine's increase [52][53][54][55][56]. Current clinical studies are evaluating to a greater extent the effect of denosumab on survival and other biomarkers.…”

Section: Zoledronic Acid and Pamidronate Activate T Cells Surveillancmentioning

confidence: 99%

Immune System and Bone Microenvironment: Rationale for Targeted Cancer Therapies

Gnoni¹,

Brunetti²,

Longo³

et al. 2019

Preprint

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Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator ok NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.

show abstract

Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials

Cited by 25 publications

References 33 publications

Comparing the Efficacy and Safety of Denosumab with Bisphosphonates in Increasing Bone Mineral Density in Patients with Prostate Cancer and Breast Cancer on Antihormonal Treatment

Comparing the Efficacy and Safety of Denosumab with Bisphosphonates in Increasing Bone Mineral Density in Patients with Prostate Cancer and Breast Cancer on Antihormonal Treatment

Immune system and bone microenvironment: rationale for targeted cancer therapies

Immune System and Bone Microenvironment: Rationale for Targeted Cancer Therapies

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