A randomised trial of 4- versus 12-weekly administration of bone-targeted agents in patients with bone metastases from breast or castration-resistant prostate cancer.

Optimal dosing of bone-targeted agents (BTAs), in patients with bone metastases remains an important clinical question. This trial compared 4-weekly versus 12-weekly therapy.

Patients with bone metastases from breast or castration-resistant prostate cancer (CRPC), who were going to start or already on BTAs, were randomised 1:1 to 4-weekly or 12-weekly BTA treatment for one year. Primary end point was change in health-related quality of life (HRQoL)-physical function European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30). Secondary end points included pain (EORTC-QLQ-BM22), global health status (EORTC-QLQ-C30), symptomatic skeletal events (SSEs) rates and time to SSEs. Primary analysis was per protocol and a non-inferiority margin of 5 points was used.

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%). Using repeated-measures analysis, across all time points, patients in the 4-weekly arm had a mean HRQL-physical subdomain score which was 1.2 (95% confidence interval: -1.6 to 4.0) higher than the 12-weekly arm. The study met the definition of non-inferiority for our primary outcome. Secondary outcomes showed no significant difference in scores for pain, global health status, SSE rates and SSE-free survival between arms. Subgroup analyses for cancer type, prior BTA use or BTA type showed no significant difference between arms.

These results in addition to those previously reported for de-escalating zoledronate and systematic reviews in both breast and prostate cancers, would support that de-escalation of commonly used BTAs is a reasonable treatment option.

European journal of cancer (Oxford, England : 1990). 2020 Oct 03 [Epub ahead of print]

Mark Clemons, Michael Ong, Carol Stober, Scott Ernst, Christopher Booth, Christina Canil, Mihaela Mates, Andrew Robinson, Phillip Blanchette, Anil Abraham Joy, John Hilton, Olexiy Aseyev, Gregory Pond, Ahwon Jeong, Brian Hutton, Sasha Mazzarello, Lisa Vandermeer, Igal Kushnir, Dean Fergusson, REaCT investigators

Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and the University of Ottawa, 501 Smyth Road, Box 912, Ottawa, Ontario, K1H 8L6, Canada; Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Box 511, Ottawa, Ontario, K1H 8L6, Canada; Clinical Epidemiology Program, The Ottawa Hospital Research Institute and University of Ottawa, 501 Smyth Road, Box 511, Ottawa, Ontario, K1H 8L6, Canada. Electronic address: ., Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and the University of Ottawa, 501 Smyth Road, Box 912, Ottawa, Ontario, K1H 8L6, Canada., Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Box 511, Ottawa, Ontario, K1H 8L6, Canada., 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, Ontario, N6A 5W9, Canada., Cancer Centre of Southeastern Ontario, 25 King Street West, Kingston, Ontario, K7L 5P9, Canada., Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2, Canada., Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and the University of Ottawa, 501 Smyth Road, Box 912, Ottawa, Ontario, K1H 8L6, Canada; Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Box 511, Ottawa, Ontario, K1H 8L6, Canada., Regional Cancer Care Northwest, Thunder Bay Regional Health Sciences Centre, 980 Oliver Road, Thunder Bay, Ontario, P7B 6V4, Canada., Department of Oncology, McMaster University, 699 Concession Street, Suite 4-204, Hamilton, Ontario, L8V 5C2, Canada., Clinical Epidemiology Program, The Ottawa Hospital Research Institute and University of Ottawa, 501 Smyth Road, Box 511, Ottawa, Ontario, K1H 8L6, Canada.