Raadpleeg ook de literatuurlijsten niet-toxische middelen en behandelingen van arts-bioloog drs. Engelbert Valstar specifiek bij borstkanker.

Zie ook in gerelateerde artikelen.

18 oktober 2023: Bron: Clinical Breast Cancer

Uit een retrospectieve studie bij totaal 224 patiënten met in de botten uitgezaaide borstkanker en die minimaal twee jaar hun borstkanker overleefden, blijkt dat het niet zoveel uitmaakt of de borstkankerpatiënten Zometa - Zoledroniczuur of Denosumab krijgen als botversterker. Beide medicijnen hadden een positief effect in het verminderen van botgerelateerde voorvallen zoals botbreuken en botschade door behandelingen op het meetpunt van 2 jaar.

In deze studie bij totaal 224 patiënten met in de botten uitgezaaide borstkanker die uitgevoerd werd in het MD Anderson ziekenhuis in Houston waren de patiënten ingedeeld in drie groepen. (1) 52 patiënten die alleen Zometa - Zoledroniczuur kregen; (2) 137 patiënten die alleen Denosumab kregen; (3) 35 patiënten die zowel ZA als denosumab kregen.

Hoewel niet statistisch significant bleek Denosumab minder botproblemen te geven in vergelijking met Zometa Zometa - Zoledroniczuur, Het totaal aantal botvoorvallen (SRE's) bedroeg 21,2% van de patiënten die alleen Zometa Zometa - Zoledroniczuur kregen, 8,8% van degenen die alleen Denosumab kregen en 20% van de patiënten die beide botversterkers kregen.

Welke botproblemen (SRE's) zich voordeden zie onderstaande grafiek, waarbij het totale aantal wel een verschil liet zien maar uitgesplitst bij de ene botversterker weer wat meer dan bij de andere en min of meer gelijk verdeeld over alle drie de groepen.

Table 2 Skeletal-related events and BTT-associated harms

Event	Zolendronic Acid	Denosumab	Both
Total SREs	10/52 (19.2%)	12/137 (8.9%)	7/35 (20%)
Pathologic fracture	4/52 (7.7%)	10/137 (7.3%)	3/35 (8.6%)
Compression fracture	4/52 (7.7%)	1/137 (0.7%)	2/35 (5.7%)
Palliative radiation	3/52 (5.8%)	1/137 (0.7%)	2/35 (5.7%)
Total BTT harms	3/52 (5.8%)	16/137 (11.7%)	5/35 (14.3%)
Osteonecrosis	3/52 (5.8%)	15/137 (10.9%)	4/35 (11.4%)
Atypical femur fracture	0/52 (05)	1/137 (0.7%)	1/35 (2.9%)

Abbreviations: SRE = skeletal-related events; BTT = bone-targeted therapy.

Zie ook Tables 3 en 4

Practische punten voor gebruik van botversterkers in de klinische praktijk:

Botversterkers (BTT), waaronder zoledroninezuur (ZA) en denosumab, verlagen het risico op skeletgerelateerde voorvallen (SRE's) bij patiënten met gemetastaseerde borstkanker (MBC) en botmetastasen.
Er ontbreken gegevens over de aantallen SRE's en door borstversterkers geassocieerde schade bij patiënten met uitgezaaide borstkanker (MBC) en botuitzaaiingen na twee jaar behandeling.
In dit retrospectieve onderzoek werden 224 patiënten met MBC en botmetastasen geanalyseerd die meer dan twee jaar lang werden behandeld, onderverdeeld in drie BTT-patronen: alleen ZA, alleen denosumab en zowel ZA als denosumab.
Deze studie vond geen verschil in totale SRE's en door botversterkers geassocieerde schade tussen deze drie behandelingsgroepen; patiënten die alleen denosumab kregen, hadden echter een verminderde onderdrukking van het ruggenmerg.
De resultaten ondersteunen de flexibiliteit wanneer een oncoloog een middel en een frequentie voor botversterkers selecteert die langer duren dan twee jaar.

Het volledige studierapport is gratis in te zien. Klik op de titel van het abstract:

Bone-Targeted Therapy Regimen and Skeletal-Related Events in Patients Surviving Longer Than 2 Years With Metastatic Breast Cancer and Bone Metastasis

Published:August 29, 2023DOI:https://doi.org/10.1016/j.clbc.2023.08.008

Abstract

Background

Bone-targeted therapy (BTT) including zoledronic acid (ZA) and denosumab decreases the risk of skeletal-related events (SREs) in patients with metastatic breast cancer (MBC) and bone metastasis. The impacts from prolonged BTT on SREs and BTT-associated harms are unknown and are becoming important to understand as these patients survive for longer periods.

Methods and Materials

We conducted a retrospective study of 224 patients with MBC and bone metastasis who survived for more than 2 years after diagnosis and received treatment at our institution between 2016 and 2021. We defined 3 BTT patterns: (1) ZA only, (2) denosumab only, (3) both ZA and denosumab. The association between these BTT patterns and SREs and harms was assessed using Fisher exact test and logistic regression.

Results

Rates of SREs overall were 21.2% of patients given ZA only, 8.8% of those given denosumab only, and 20% of those given both, without statistically significant differences (p = .32). However, those treated with denosumab only had significantly fewer compression fractures (0.7%) (p = .02). BTT-associated harm was observed in 5.8% of the ZA-only group, 11.7% of the denosumab-only group, and 14.3% of the group given both, without statistically significant differences (p = .37).

Conclusion

Oncologists may have increased flexibility regarding the frequency of administration of BTT along with their choice of agent. Our study showed no significant difference in the prevention of overall SRE or development of BTT-associated harms between the BTT regimens evaluated.

Clinical Practice Points

•
Bone-targeted therapy (BTT) agents including zoledronic acid (ZA) and denosumab decrease the risk of skeletal-related events (SREs) in patients with metastatic breast cancer (MBC) and bone metastasis.
•
Data are lacking regarding the rates of SREs and BTT-associated harms in patients with MBC and bone metastasis beyond 2 years of treatment.
•
This retrospective study analyzed 224 patients with MBC and bone metastasis who received treatment for more than 2 years, categorized into 3 BTT patterns: ZA only, denosumab only, and both ZA and denosumab.
•
Thiis study found no difference in overall SREs and BTT-associated harms between these 3 treatment groups; however, patients who received denosumab only did have reduced rates of spinal cord compression.
•
Results supports flexibility when an oncologist selects an agent and a frequency for BTT regimens extending beyond 2 years.

Data Availability Statement

The data that support the findings of this study are available by request from the corresponding author.

Previous Presentations

The abstract of this study was presented as an online abstract at the ASCO 2022 meeting.

Ethics Statement

The University of Texas MD Anderson Cancer Center institutional review board approved this investigation (IRB #2021-0541, date of approval: 6/1/2021). A waiver of informed consent was granted by the institutional review board.

Acknowledgments

This research was supported by the National Cancer Institute through The University of Texas MD Anderson's Cancer Center Support Grant (P30CA016672). We thank Ashli Nguyen-Villarreal, Associate Scientific Editor, and Sarah Bronson, Scientific Editor, in the Research Medical Library at The University of Texas MD Anderson Cancer Center, for editing this article.

Disclosure

All authors declare no conflict of interest.

References

- Siegel RL
- Miller KD
- Jemal A
Cancer statistics, 2020.
CA Cancer J Clin. 2020; 70: 7-30
View in Article
- Gradishar WJ
- Moran MS
- Abraham J
- et al.
Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.
J Natl Compr Canc Netw. 2022; 20: 691-722
View in Article
- Van Poznack C
- Somerfield MR
- Barlow W
- et al.
Role of bone modifying agents in metastatic breast cancer: an American Society of Clinical Oncology - Cancer Care Ontario Focused Guideline update.
J Clin Oncol. 2017; 35: 3978-3986
View in Article
- Goldvaser H
- Amir E
Role of bisphosphonates in breast cancer therapy.
Curr Treat Options Oncol. 2019.; 20: 1-17
View in Article
- Khan AA
- Morrison A
- Hanley DA
- et al.
Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus.
J Bone Miner Res. 2015; 30: 3-23
View in Article
- Steger GG
- Bartsch R
Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion.
Ther Adv Med Oncol. 2011; 3: 233-243
View in Article
- Hortobagyi GN
- Van Poznak C
- Harker WG
- et al.
Continued treatment effect of zoledronic acid dosing every 12 vs 4 weeks in women with breast cancer metastatic to bone: the OPTIMIZE-2 randomized clinical trial.
JAMA Oncol. 2017; 3: 906-912
View in Article
- Amadori D
- Aglietta M
- Alessi B
- et al.
Efficacy and safety of 12-weekly versus 4-weekly zoledronic acid for prolonged treatment of patients with bone metastases from breast cancer (ZOOM): a phase 3, open-label, randomised, non-inferiority trial.
Lancet Oncol. 2013; 14: 663-670
View in Article
- Himelstein AL
- Foster JC
- Khatcheressian JL
- et al.
Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases.
A Randomized Clinical Trial JAMA. 2017; 317: 48-58
View in Article
- Google Scholar
- O’Carrigan B
- Wong MH
- Willson ML
- et al.
Bisphosphonates and other bone agents for breast cancer.
Cochrane Lib. Rev. 2017; 10: 1-167
View in Article
- Google Scholar
- Quispe D
- Shi R
- Burton G
Osteonecrosis of the jaw in patients with metastatic breast cancer: ethnic and socio-economic aspects.
The Breast Journal. 2011; 17: 510-513
View in Article
- Wutzl A
- Eisenmenger G
- Hoffmann M
- et al.
Osteonecrosis of the jaws and bisphosphonate treatment in cancer patients.
Wiener Klinische Wochenschrift. 2006; 118: 473-478
View in Article
- Edwards BJ
- Sun M
- West DP
- et al.
Incidence of atypical femur fractures in cancer patients: the MD Anderson Cancer Center experience.
J Bone Miner Res. 2016; 31: 1569-1576
View in Article
- Sinha AK
- Patel JR
- Shen Y
- et al.
Location of receipt of initial treatment and outcomes in long-term breast cancer survivors.
PLoS One. 2017; 12e0170081
View in Article
- Edge SB
- Compton CC
The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.
Ann Surg Oncol. 2010; 17: 1471-1474
View in Article
- Singletary SE
- Allred C
- Ashley P
- et al.
Staging system for breast cancer: revisions for the 6th edition of the AJCC Cancer Staging Manual.
Surgical Clinics. 2003; 83: 803-819
View in Article
- Hammond ME
- Hayes DF
- Dowsett M
- et al.
American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.
J Clin Oncol. 2010; 28: 2784-2795
View in Article
- Carlson RW
- Moench SJ
- Hammond ME
- et al.
HER2 testing in breast cancer: NCCN Task Force report and recommendations.
J Natl Compr Canc Netw. 2006; 4 (quiz S23-4): S1-22
View in Article
- PubMed
- Google Scholar
- Wolff AC
- Hammond ME
- Hicks DG
- et al.
Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.
J Clin Oncol. 2013; 31: 3997-4013
View in Article
- Coleman RE
Bisphosphonates: clinical experience.
Oncologist. 2004; 9: 14-27
View in Article
- Facchini G
- Caraglia M
- Santini D
- et al.
The clinical response on bone metastasis from breast and lung cancer during treatment with zoledronic acid is inversely correlated to skeletal related events (SRE).
J Exp Clin Cancer Res. 2007; 26: 307-312
View in Article
- PubMed
- Google Scholar
- Kohno N
- Aogi K
- Minami H
- et al.
Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial.
J Clin Oncol. 2005; 23: 3314-3321
View in Article
- Lipton A
- Steger GG
- Figueroa J
- et al.
Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy.
Clin Cancer Res. 2008; 14: 6690-6696
View in Article
- Stopeck AT
- Fizazi K
- Body J-J
- et al.
Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer.
Supportive Care Cancer. 2016; 24: 447-455
View in Article
- Friedl TWP
- Fehm T
- Müller V
- et al.
Prognosis of patients with early breast cancer receiving 5 years vs 2 years of adjuvant bisphosphonate treatment: a phase 3 randomized clinical trial.
JAMA Oncol. 2021; 7: 1149-1157
View in Article
- Ibrahim M
- Mazzarello S
- Shorr R
- et al.
Should de-escalation of bone-targeting agents be standard of care for patients with bone metastases from breast cancer? A systematic review and meta-analysis.
Ann Oncol. 2015; 26: 2205-2213
View in Article
- Tesfamariam Y
- Jakob T
- Wöckel A
- et al.
Adjuvant bisphosphonates or RANK-ligand inhibitors for patients with breast cancer and bone metastases: a systematic review and network meta-analysis.
Crit Rev Oncol/Hematol. 2019; 137: 1-8
View in Article
- Stopeck AT
- Lipton A
- Body J-J
- et al.
Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study.
J Clin Oncol. 2010; 28: 5132-5139
View in Article
- Martin M
- Bell R
- Bourgeois H
- et al.
Bone-related complications and quality of life in advanced breast cancer: results from a randomized phase III trial of denosumab versus zoledronic acid.
Clin Cancer Res. 2012; 18: 4841-4849
View in Article
- Abdel-Rahman O
Denosumab versus zoledronic acid to prevent aromatase inhibitors-associated fractures in postmenopausal early breast cancer: a mixed treatment meta-analysis.
Expert Rev Anticancer Ther. 2016; 16: 885-891
View in Article
- Lipton A
- Fizazi K
- Stopeck AT
- et al.
Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics.
Eur J Cancer. 2016; 53: 75-83
View in Article
- Lipton A
- Fizazi K
- Stopeck AT
- et al.
Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials.
Eur J Cancer. 2012; 48: 3082-3092
View in Article
- Al Farii H
- Frazer A
- Farahdel L
- et al.
Bisphosphonates versus denosumab for prevention of pathological fracture in advanced cancers with bone metastasis: a meta-analysis of randomized controlled trials.
JAAOS Global Res Rev. 2020; 4
View in Article
- Wu E
- Xie J
- Signorovitch J
- et al.
Number needed to treat and treatment cost per fracture avoided with denosumab compared with zoledronic acid in patients with breast cancer with bone metastases.
J Clin Oncol. 2011.; 29: 151
View in Article
- Crossref
- Google Scholar
- Coleman RE
Bisphosphonates: clinical experience.
Oncologist. 2004; 9: 14-27
View in Article
- Rosen LS
- Gordon D
- Kaminski M
- et al.
Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial.
Cancer. 2003; 98: 1735-1744
View in Article
- Body J-J
- Diel IJ
- Bell R
- et al.
Oral ibandronate improves bone pain and preserves quality of life in patients with skeletal metastases due to breast cancer.
Pain. 2004; 111: 306-312
View in Article
- Barrett-Lee P
- Casbard A
- Abraham J
- et al.
Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone metastases from breast cancer: a randomised, open label, non-inferiority phase 3 trial.
Lancet Oncol. 2014; 15: 114-122
View in Article