Comparing Continuation or De-escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases From Either Breast or Castration-resistant Prostate Cancer

Health related quality of life (HR-QoL) scores measured by the European Organisation for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ)-C30 physical functioning subscale and the European Organisation for Research and Treatment of Cancer (EORTC)- Quality of Life Questionnaire (QLQ)- for patients with bone metastasis (BM)22 functional interference subscale. The EORTC-QLQ-C30 is an internationally accepted and validated tool in multiple large study cohorts capturing HR-QoL from a multi-dimensional and global perspective in oncology. EORTC-QLQ-BM22 has been validated for use specifically in bone metastases. They were developed in collaboration with patients, healthcare professionals and thorough review of the literature, and therefore important to all stakeholders; the scales are well-defined and easily measured, and HR-QoL is a relevant goal of care in the palliative care setting.

Number of patients with one or more SSEs (defined as: use of radiotherapy to relieve skeletal symtoms, new symptomatic pathological bone fractures [vertebral or non-vertebral], spinal cord compression, tumour-related orthopedic surgical intervention, or hypercalcaemia] during trial period) up to 2 years post-randomization.

Defined from the date of randomization until the first date of patient experience an SSE. Any patient who does not experience an SSE will be censored on the last follow-up date and the patient can be confirmed as SSE-free (up to 2 years).

SSE-free survival (composite of time to first SSE and time to death)

Skeletal morbidity rate defined as ration of number of SSEs for each subject divided by the subject's time at risk in years.

Assess quality of life of cancer patients using the EORTC-QLQ-C30 (cancer patient specific questionnaire) at each time point, up to and including 48 weeks ("one year of treatment")

Assess quality of life of cancer patients using the EORTC-QLQ-BM22 (patients with bone metastases specific questionnaire) at each time point, up to and including 48 weeks ("one year of treatment")

BMA-related toxicity rates (up to 2 years) based on standard of care blood tests and clinical assessments

Defined as the difference in cost between two possible interventions, divided by the difference in their Quality Adjusted Life Year (QALY) gained.

In the continuation arm, frequency of subsequent de-escalation or discontinuation of BMAs

In the de-escalation arm, frequency of restarting standard dosing BMA (and the reasons for restarting)

Overall survival during study duration