Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials

Kroep, Judith R.; Charehbili, Ayoub; Coleman, Robert E.; Aft, Rebecca; Hasegawa, Yoshie; Winter, M.C.; Weilbaecher, Katherine N.; Akazawa, Kohei; Hinsley, Samantha; Putter, Hein; Liefers, Gerrit‐Jan; Nortier, J.W.R.; Kohno, Norio

doi:10.1016/j.ejca.2015.10.011

Cited by 28 publications

(25 citation statements)

References 22 publications

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“…However, this effect was only seen in postmenopausal and not in premenopausal women [86]. In the neoadjuvant setting, a similar trend was observed in postmenopausal patients [87].…”

Section: An Anti-tumor Effect Of Rankl Inhibition Mediated Via the Immentioning

confidence: 86%

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

Groot

Appelman‐Dijkstra

Burg

et al. 2018

Cancer Treatment Reviews

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101

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At present, accumulating evidence suggests that inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) does not only induce an increase in bone mass and strength, but also has anti-tumor effects. Denosumab, an antibody targeting RANKL, is used to treat osteoporosis and to prevent skeletal related events (SREs) in patients with bone metastases originating from solid tumors. However, expression of RANKL and its receptor activator of nuclear factor kappa-B (RANK) is not solely restricted to cells involved in homeostasis of the bone and RANKL-RANK signalling appears to play a substantial role in many other processes in the body like mammary physiology, mammary tumorigenesis and the immune system. In pre-clinical models, RANKL inhibition has been shown to reduce skeletal tumor burden and distant metastases as well as to decrease mammary carcinogenesis. Clinically, RANKL inhibition improves bone-metastasis free survival in patients with prostate cancer and disease-free survival in patients with breast cancer. In addition, RANKL treatment may form a preventative strategy in patients at high risk for malignancies of the breast. Current clinical studies are evaluating the effect of denosumab on survival, the immune system and other biomarkers into a greater extent. To that purpose, a systematic review of the literature was performed and a narrative review synthesized, describing the present pre-clinical and clinical evidence of an anti-tumor effect of RANKL inhibition and the potential role of the immune system as one of the underlying mechanisms.

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“…However, this effect was only seen in postmenopausal and not in premenopausal women [86]. In the neoadjuvant setting, a similar trend was observed in postmenopausal patients [87].…”

Section: An Anti-tumor Effect Of Rankl Inhibition Mediated Via the Immentioning

confidence: 86%

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

Groot

Appelman‐Dijkstra

Burg

et al. 2018

Cancer Treatment Reviews

Self Cite

101

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“…Also, this study's meta-analysis provides the first data indicating a statistically significant benefit of the addition of ZOL to neoadjuvant CT in terms of pCR in postmenopausal patients with early breast cancer. The addition of ZOL to systemic therapy has shown a survival benefit in postmenopausal patients with low levels of reproductive hormones [17].…”

Section: Discussionmentioning

confidence: 99%

Cost-Effectiveness Analysis of Neoadjuvant Chemotherapy with Zoledronic Acid for HER2-Negative Breast Cancer in Japan: The JONIE1 Study

Nakazawa¹,

Saito²,

Nagahashi³

et al. 2019

Health

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Objective: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption. Adding ZOL to neoadjuvant chemotherapy has been shown to have potential anticancer benefits in women with HER2-negative breast cancer. The objective of the present study was to investigate ZOL's cost-effectiveness from the perspective of health care payers in Japan. Methods: A Markov model was developed to evaluate the costs and effectiveness associated with ZOL + chemotherapy (CTZ) and chemotherapy (CT) alone over a 10-year time horizon. Monthly transition probabilities were estimated according to JONIE1 (Japan Organization of Neoadjuvant Innovative Expert) Study data and an extrapolated Weibull model. Health outcomes were measured in quality-adjusted life years (QALYs). Costs were calculated using year-2018 Japanese yen (JPY) (1.00 US dollars (USD) = 110.4 JPY). Model robustness was addressed through one-way and probabilistic sensitivity analysis. The costs and QALYs were discounted at a rate of 2% per year. Results: In the base case, the use of CTZ was associated with a gain of 3.94 QALYs. The incremental cost per QALY of the CTZ gain was 681,056.1 JPY (6168.99 USD) per QALY. Conclusion: It is convincing that neoadjuvant CTZ for patients with breast cancer would be expected to have statistically significant clinical efficacy. Addition of ZOL to CT might be a cost-effective option compared with CT alone.

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“…ZOL antiangiogenic effects in a neoadjuvant setting were also suggested, in prostate cancer patients, where ZOL treatment decreased the number of circulating endothelial and endothelial precursor cells, both markers of ongoing pathological neoangiogenesis [38]. Additionally, a meta-analysis of randomized trials of ZOL plus neoadjuvant chemotherapy in breast cancer patients revealed benefits in terms of pathological complete response in the breast only for postmenopausal women [39].…”

Section: Table 1 Bisphosphonate Classes and Their Anti-tumour And/ormentioning

confidence: 96%

Bone-Targeted Therapies in Cancer-Induced Bone Disease

Sousa

Clézardin

2017

Calcif Tissue Int

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Cancer-induced bone disease is a major source of morbidity and mortality in cancer patients. Thus, effective bone-targeted therapies are essential to improve disease-free, overall survival and quality of life of cancer patients with bone metastases. Depending of the cancer-type, bone metastases mainly involve the modulation of osteoclast and/or osteoblast activity by tumour cells. To inhibit metastatic bone disease effectively, it is imperative to understand its underlying mechanisms and identify the target cells for therapy. If the aim is to prevent bone metastasis, it is essential to target not only bone metastatic features in the tumour cells, but also tumour-nurturing bone microenvironment properties. The currently available bone-targeted agents mainly affect osteoclasts, inhibiting bone resorption (e.g. bisphosphonates, denosumab). Some agents targeting osteoblasts begin to emerge which target osteoblasts (e.g. romosozumab), activating bone formation. Moreover, certain drugs initially thought to target only osteoclasts are now known to have a dual action (activating osteoblasts and inhibiting osteoclasts, e.g. proteasome inhibitors). This review will focus on the evolution of bone-targeted therapies for the treatment of cancer-induced bone disease, summarizing preclinical and clinical findings obtained with anti-resorptive and bone anabolic therapies.

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Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials

Cited by 28 publications

References 22 publications

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

Cost-Effectiveness Analysis of Neoadjuvant Chemotherapy with Zoledronic Acid for HER2-Negative Breast Cancer in Japan: The JONIE1 Study

Bone-Targeted Therapies in Cancer-Induced Bone Disease

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