BMB are independently prognostic for survival in men with metastatic castration resistant PC. It is unclear whether prognostic or predictive value of BMB applies to an earlier HSPC state. We prospectively assessed BMB in men enrolled in S1216, a phase III trial of ADT +/- orteronel with an ultimate goal to identify HSPC patient (pt) subsets defined by BMB that have differential survival outcomes. Here we report initial results of baseline BMB from S1216 & their relationship to clinical variables.
Bone resorption [C-telopeptide(CTx) & Pyridinoline (PYD)] & formation markers [C-terminal collagen propeptide (CICP) & bone alkaline phosphatase (BAP)] were measured. Elevated BMB was defined as above median or in upper quartile for each BMB. Men were grouped as having all four, 1-3, or no BMB elevated. Frequency tables of BMB distribution across pt subsets were generated. To account for multiple comparisons, a p-value of < 0.001 was considered potentially significant.
Of 1,313 men, 799 had baseline BMB. Pt characteristics [median (range) or n (%)]: age 67y (19-92); PSA 29 ng/dL (2-6710); Gleason >7: n = 479 (64%); bone mets: 604 (76%); bisphos/denosumab: 44 (5.5%); Zubrod PS 0: 547 (68%); & minimal disease extent: 389 (49%). Median BMB: CTx 0.46 ng/mL (0.03-12.2); PYD 1.68 nmol/L (0.35-17.5); CICP 116 ng/mL (0.25-3360); BAP 1.66 u/L (0-1001). At least one BMB was > median in 87% & in top quartile in 57%. In 604 w/ bone mets, 540 had at least 1 BMB > median while distribution of BMB elevation >median differed significantly w/in groups defined by PSA (p < 0.0001), Gleason score (p = 0.0001), PS (p < 0.0001) & disease extent (p < 0.0001). For example, in 292 with PSA>29, 30% had all 4 BMB elevated; in those with PSA < 29, only 6% had all 4 elevated. BMB distribution in all men did not differ within race/ethnicity, age, & bisphos/denosumab groupings. Trends were similar when BMB upper quartile was used.
In men with HSPC initiating ADT, at least one BMB was elevated in 87%. Differences in BMB distribution were seen within pre-defined subsets, with BMB elevation tracking with higher tumor grade, disease burden & lower PS. Assessment of BMB association with patient outcomes is planned.
Clinical trial identification
SWOG S1216; NCT01809691.
Legal entity responsible for the study
NIH/NCI grants CA180888, CA180819; and Millennium Pharmaceuticals (Takeda Oncology Company) NIH.
All authors have declared no conflicts of interest.