A Study to Compare Denosumab With Zoledronic Acid in Subjects With Bone Metastases From Solid Tumors

uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment (trt). uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Primary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in par. of Asian ancestry with bone metastases from solid tumors. BL value is the most recent, non-missing value prior to or on the 1st study trt dose date. Chg from BL is the value at Wk13 minus BL value. Percent chg from BL is the chg from BL / BL value \* 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value.

Time frame: Baseline (BL) and Week (Wk) 13

Population: Full-Analysis-Set Intent-to-Treat (FAS-ITT) Population: comprised of all randomized participants regardless of whether or not study treatment was administered. Only those participants with values at Baseline and Week 13 were included in the analysis.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or other events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcome listed above, liver injury and impaired liver function and grade 4 laboratory abnormalities. Number of participants with any AEs, non-fatal SAEs, fatal SAEs have been presented.

Time frame: From start of IP through the Study Phase (49 weeks post-dose) (assessed up to 73 weeks)

Population: Full-Analysis-Set Safety (FAS-Safety) Population: comprised of all randomized participants who received at least one dose of study treatment and was based on the actual study treatment received (if this differed from that to which the participant was randomized).

Anti-denosumab antibody formation was assessed at Day 1, Week 25 and Week 53. Binding antibody assay was used to assess number of participants with anti-denosumab antibody.

Time frame: Day 1, Week 25 and Week 53

Population: FAS-Safety Population. Only those participants on whom anti-denosumab antibody formation was analyzed at specified time point is presented (represented by n=X, X in the category titles).

Hematology parameters included hemoglobin, lymphocytes, platelet count, total neutrophils, white blood cell (WBC) count. All reported values are of participants with worst-case on-therapy increase to the specified grade: Any increase, that is, worst-case increase to grade 1, 2, 3, or 4 (any grade); worst-case increase to grade 3 (WC G3); and worst-case increase to grade 4 (WC G4). Participants with missing Baseline grade were assumed to have a Baseline grade of 0. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.

Time frame: Baseline and up to last study-related visit (up to 53 weeks)

Population: FAS-Safety Population. Only participants whose indicated on-therapy lab values were available (represented by n=X, X in the category titles) were analyzed.

Clinical chemistry parameters were measured at the Screening and Weeks 2, 5, 9, 13, 25, 37, and 53 visits. Clinical chemistry parameters measured on-study included albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, calcium (Ca), creatinine, magnesium, and phosphorous (P) inorganic. All reported values are of participants with worst-case on-therapy increase to the specified grade: Any increase, that is, worst-case increase to grade 1, 2, 3, or 4 (any grade); worst-case increase to grade 3 (WC G3); and worst-case increase to grade 4 (WC G4). The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) was used for grading. Participants with missing Baseline grade were assumed to have a Baseline grade of 0. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.

Time frame: Baseline and up to last study-related visit (up to 53 weeks)

Population: FAS-Safety Population. Only participants whose indicated on-therapy laboratory values were available (represented by n=X, X in the category title) were analyzed.

uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment. uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Secondary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in par. of Chinese ancestry with bone metastases from solid tumors. Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Week 13 minus Baseline value. Percent chg from BL is the chg from BL / BL value \* 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value.

Time frame: Baseline and Week 13

Population: FAS-ITT Population. Chinese participants.

uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment. uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Secondary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in breast cancer par. with bone metastases from solid tumors. Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Week 13 minus Baseline value. Percent chg from BL is the chg from BL / BL value \* 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value.

Time frame: Baseline and Week 13

Population: FAS-ITT Population. Participants with advanced breast cancer.

Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Indicated visit minus Baseline value. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100.

Time frame: Baseline and Week 13

Population: FAS-ITT Population. All participants who were randomized and had a observed values at Baseline and Week 13 were used in the analysis.

Blood samples were drawn on study Day 1, pre-dose; 4 hours, 24 hours, and at Week 2 (168 hours); then pre-dose at Week 5, Week 9, Week 13, Week 17, Week 19 (no dose), Week 21, Week 25, and Week 49.

Time frame: Samples were collected at pre-dose (Day 1); 4 hours, 24 hours, 168 hours post-dose; pre-dose at Week 5, Week 9, Week 13, Week 17; Week 19 (at 336 hours); pre-dose at Week 21, Week 25, Week 49

Population: Pharmacokinetic (PK) Population: comprised of participants who signed informed consent to participate in the PK sub-study and who had their PK parameters evaluable according to GSK standards. Only those participants with evaluable parameters are included (represented by n=X in the category titles).