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

Background: 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 and methods: 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. 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%). 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 SSEfree survival between arms. Subgroup analyses for cancer type, prior BTA use or BTA type showed no significant difference between arms. Conclusion: These results in addition to those previously reported for de-escalating zoledronate and systematic reviews in both breast and prostate cancers, would support that deescalation of commonly used BTAs is a reasonable treatment option. (C) 2020 The Author(s). Published by Elsevier Ltd.

Automated summary

The study compared the efficacy of bone-targeted agents (BTAs) given every 4 weeks versus 12 weeks in patients with bone metastases from breast or castration-resistant prostate cancer. The results showed no significant difference in health-related quality of life, pain, global health status, rates of symptomatic skeletal events, and time to symptomatic skeletal events between the two dosing regimens. The findings suggest that de-escalation of commonly used BTAs is a viable treatment option.