Endpoint comparison for osteoporosis assessment in cancer control studies (N02C1 and N03CC)

Abstract

6627 Background: Methodological issues hamper efficacy assessment of agents to prevent osteoporosis in cancer survivors. The diagnosis of osteoporosis can vary depending upon which bone mineral density (BMD) site is used, which machine is used for the assessment, and which set of normative values are applied. This analysis compared different endpoints for the assessment of efficacy in 2 cancer control studies. Methods: Data from 2 NCCTG phase 3 cancer control studies were employed involving 216 (N02C1) and 558 (N03CC) patients each comparing 2 treatments for the prevention of osteoporosis. BMD data were collected from spine (primary endpoint), femoral neck, and total hip. Endpoints included raw BMD score (RawBMD); raw machine-based T-score (TRaw); sample-standardized T-score (TSamp); reference population standardized T-score (TRef); and Z-score percentile corresponding to TRef (TPerc). For each of the 5 endpoints, summary statistics were computed and the analytical comparison of treatment arms was carried out via Student's t-test, Wilcoxon rank-sum, and baseline BMD-adjusted ANCOVA using change from baseline (CB) and percentage change of baseline (%CB) at 1 year. Each study was analyzed separately. Results: Results differed by BMD site and whether CB or %CB was used (table below). Among the 5 endpoints, TRaw, TSamp, and TRef had 11, 8, and 7 statistically significant results out of 36 tests, respectively. TPerc and RawBMD produced the most statistically significant results, 13 and 14, respectively. Correlations among the 5 endpoints at baseline ranged from .79 to >.99. Conclusions: Treatment comparisons differed across BMD site and endpoint used. Transforming via sample statistics provided similar results to transforming via reference or machine norms. RawBMD and the new approach (TPerc) may be more sensitive to change with TPerc having the added benefit of being readily interpretable as a percentage. No. of significant tests (out of 15) N02C1 N03CC CB %CB CB %CB Spine 4 1 15 6 Femoral Neck 1 0 15 3 Total Hip 0 0 7 1 No significant financial relationships to disclose.