Two-year results of a randomised trial comparing 4- versus 12-weekly bone-targeted agent use in patients with bone metastases from breast or castration-resistant prostate cancer

Mark Clemons^{1

2}, Michelle Liu², Carol Stober², Gregory Pond³, Mashari Jemaan Alzahrani¹, Michael Ong¹, Scott Ernst⁴, Christopher Booth⁵, Mihaela Mates⁵, Anil Abraham Joy⁶, Olexiy Aseyev⁷, Phillip Blanchette⁴, Lisa Vandermeer², Megan Tu², Kednapa Thavorn^{8

9}, Dean Fergusson⁸; REaCT investigators

Affiliations

¹ Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and the University of Ottawa, 501 Smyth Road, Box 912, Ottawa, ON K1H 8L6, Canada.
² Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Box 511, Ottawa, ON K1H 8L6, Canada.
³ Department of Oncology, McMaster University, 699 Concession Street, Suite 4-204, Hamilton, ON L8V 5C2, Canada.
⁴ Division of Medical Oncology, Department of Oncology, London Regional Cancer Program, London Health Sciences Centre and University of Western Ontario, 800 Commissioners Road East, London, ON N6A 5W9, Canada.
⁵ Cancer Centre of Southeastern Ontario, 25 King Street West, Kingston, ON K7L 5P9, Canada.
⁶ Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada.
⁷ Regional Cancer Care Northwest, Thunder Bay Regional Health Sciences Centre, 980 Oliver Road, Thunder Bay, ON P7B 6V4, Canada.
⁸ Clinical Epidemiology Program, Ottawa Hospital Research Institute, and the University of Ottawa, Ottawa, ON K1H 8L6, Canada.
⁹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1G 5Z3, Canada.

PMID: 34567960
PMCID: PMC8449269
DOI: 10.1016/j.jbo.2021.100388

Two-year results of a randomised trial comparing 4- versus 12-weekly bone-targeted agent use in patients with bone metastases from breast or castration-resistant prostate cancer

Mark Clemons et al. J Bone Oncol. 2021.

. 2021 Sep 2:30:100388.

doi: 10.1016/j.jbo.2021.100388. eCollection 2021 Oct.

Authors

Affiliations

¹ Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and the University of Ottawa, 501 Smyth Road, Box 912, Ottawa, ON K1H 8L6, Canada.
² Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Box 511, Ottawa, ON K1H 8L6, Canada.
³ Department of Oncology, McMaster University, 699 Concession Street, Suite 4-204, Hamilton, ON L8V 5C2, Canada.
⁴ Division of Medical Oncology, Department of Oncology, London Regional Cancer Program, London Health Sciences Centre and University of Western Ontario, 800 Commissioners Road East, London, ON N6A 5W9, Canada.
⁵ Cancer Centre of Southeastern Ontario, 25 King Street West, Kingston, ON K7L 5P9, Canada.
⁶ Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada.
⁷ Regional Cancer Care Northwest, Thunder Bay Regional Health Sciences Centre, 980 Oliver Road, Thunder Bay, ON P7B 6V4, Canada.
⁸ Clinical Epidemiology Program, Ottawa Hospital Research Institute, and the University of Ottawa, Ottawa, ON K1H 8L6, Canada.
⁹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1G 5Z3, Canada.

PMID: 34567960
PMCID: PMC8449269
DOI: 10.1016/j.jbo.2021.100388

Abstract

Background: We present the 2-year results of a randomised trial comparing 4- versus 12-weekly bone-targeting agents (BTAs) in patients with bone metastases from breast or castration-resistant prostate cancer (CRPC).

Patients and methods: Patients with bone metastases from breast or CRPC, who were going to start or were already receiving BTAs, were randomised to 4- or 12-weekly BTA treatment for 2 years. The endpoints were: symptomatic skeletal events (SSE) rates, time to SSEs, toxicity and cost-effectiveness.

Results: Of 263 patients (160 breast cancer, 103 CRPC), 133 (50.6%) and 130 (49.4%) were randomised to the 4- and 12-weekly groups, respectively. BTAs included denosumab (56.3%), zoledronate (24.0%) and pamidronate (19.8%). After 2 years, the cumulative incidence rate (95% CI) of SSEs was 32.7% (24.6% to 41.1%) and 28.1% (20.3% to 36.4%) for the 4- and 12-weekly intervention groups respectively. The hazard ratio for time to first SSE was 0.96 (95% CI = 0.63 to 1.47). However, in a post hoc analysis, those patients who had an on-study SSE, there was a small non-statistical increased risk of subsequent SSEs among patients on the 12-weekly dosing arm (HR = 1.14; 95% CI - 0.90-1.44). BTA-related toxicity rates were similar between study arms. A cost-utility analysis showed that 12-weekly BTA is cost-effective from a public payer's perspective.

Conclusion: These results in addition to those previously reported for de-escalating zoledronate, would support that de-escalation of commonly used BTAs is a reasonable and economically valid treatment option. While not statistically significant, the increase in subsequent SSEs in the 12-weekly arm requires further exploration.

Keywords: Bisphosphonates; Breast cancer; Denosumab; Prostate cancer.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 2**
Cumulative incidence of first SSE.

**Fig. 3**
One-year (95% CI) SSE-free survival by study group, bone-targeted agent and tumour type. SSE, symptomatic skeletal event.

**Fig. 4**
SSE events in the 4-weekly (Fig a) and 12-weekly (Fig b) arms.

**Fig. 5**
Deterministic sensitivity analysis results.

**Fig. 6**
Probabilistic sensitivity analysis results.

See this image and copyright information in PMC

References

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Two-year results of a randomised trial comparing 4- versus 12-weekly bone-targeted agent use in patients with bone metastases from breast or castration-resistant prostate cancer

Affiliations

Two-year results of a randomised trial comparing 4- versus 12-weekly bone-targeted agent use in patients with bone metastases from breast or castration-resistant prostate cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources