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

• Published in: European journal of cancer (1990) 2021-01, Vol.142, p.132-140
• Main Authors: Clemons, Mark, Ong, Michael, Stober, Carol, Ernst, Scott, Booth, Christopher, Canil, Christina, Mates, Mihaela, Robinson, Andrew, Blanchette, Phillip, Joy, Anil Abraham, Hilton, John, Aseyev, Olexiy, Pond, Gregory, Jeong, Ahwon, Hutton, Brian, Mazzarello, Sasha, Vandermeer, Lisa, Kushnir, Igal, Fergusson, Dean
• Format: Article
• Language: English
• Subjects: Aged; Bisphosphonates; Bone Density Conservation Agents - pharmacology; Bone Density Conservation Agents - therapeutic use; bone metastasis; Bone Neoplasms - secondary; Breast cancer; Breast Neoplasms - complications; Breast Neoplasms - drug therapy; Castration; Clinical Trial; Confidence intervals; denosumab; Drug Administration Schedule; Female; Global health; Humans; Literature reviews; Male; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; Pain; pamidronate; Pamidronic acid; Patients; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - complications; Prostatic Neoplasms, Castration-Resistant - drug therapy; Public health; Quality of life; Subgroups; Targeted cancer therapy; zoledronate; Zoledronic acid
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2020.08.019

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. •Four- versus 12-weekly therapy of bone-targeting agents in patients with bone metastases from breast or prostate cancer.•BTAs used in the study are pamidronate, zoledronate and denosumab.•Twelve-weekly therapy was non-inferior to 4-weekly therapy for the primary outcome of health-related quality of life.•No significant difference was seen in symptomatic skeletal event (SSE) rates and SSE-free survival between arms.•Results consistent with previous studies, suggests that de-escalation of BTAs is a reasonable treatment option.