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; Michelle Liu; Carol Stober; Gregory Pond; Mashari Jemaan Alzahrani; Michael Ong; Scott Ernst; Christopher Booth; Mihaela Mates; Anil Abraham Joy; Olexiy Aseyev; Phillip Blanchette; Lisa Vandermeer; Megan Tu; Kednapa Thavorn; Dean Fergusson; REaCT investigators

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

J Bone Oncol. 2021 Sep 2:30:100388. doi: 10.1016/j.jbo.2021.100388. eCollection 2021 Oct.

Authors

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.

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.