Citations

LBA500 Background: The primary endpoint of NSABP B-35, a phase III trial comparing 1 mg/day anastrozole to 20 mg/day tamoxifen, each given for 5 years, was breast cancer-free interval (BCFI), defined as the time from randomization to any breast cancer (BC) event including local, regional, or distant recurrence or contralateral disease, invasive or DCIS. Methods: Postmenopausal women with ER-receptor or PgR-receptor positive (by IHC analysis) DCIS and no invasive BC who had undergone a lumpectomy with clear resection margins were randomly assigned to receive either 20 mg/day tam or 1 mg/day A (blinded) for 5 years. Stratification was by age (<60 v ≥60). Results: From 1/6/2003 to 6/15/2006, 3,104 pts were entered and randomized (1552 in groups tam and A each). As of 2/28/15, follow-up information was available on 3,083 pts for OS and on 3,077 pts for all other disease-free endpoints, with mean time of follow-up of 8.6 years. There were 198 BCFI events, 114 in the tam group and 84 in the A group (HR, 0.73; p=0.03). 10-year point estimates for BCFI were 89.2% for tam and 93.5% for A. A significant time-by-treatment interaction (p=0.02) indicated that the effect was not evident until later in the study. There was a significant interaction between treatment and age group (p=0.04); benefit of A is only in women <60 years old. As to secondary endpoints, there were 495 DFS events, 260 in the tam group and 235 in the A group (HR, 0.89; p=0.21). 10-year point estimates for DFS were 77.9% for tam and 82.7% for A. There were 186 deaths, 88 in the tam group and 98 in the A group (HR, 1.11; p=0.48). 10-year point estimates for OS were 92.1% for tam, 92.5% for A. There were 8 deaths due to breast cancer in the tam group and 5 in the A group. There were 63 cases of invasive breast cancer in the tam group and 39 in the A group (HR, 0.61; p=0.02). There was a non-significant trend for a reduction in breast second primary cancers with A (HR, 0.68; p=0.07). Conclusions: Anastrozole provided a significant improvement compared to tamoxifen for BCFI, which was seen later in the study, primarily in women <60 years. Support: CA12027, 37377, 69651, 69974; 180868, 180822, 189867 196067, 114732; AstraZeneca Pharmaceuticals LP. Clinical trial information: NCT00053898.

Abstract Background The clinical results of NSABP B-35, phase III trial comparing 1 mg/day A to 20 mg/day tam, each given for 5 years, were reported at ASCO 2015. B-35 demonstrated a statistically significant benefit in breast cancer free interval for women assigned to A, primarily in women &lt;60 years. A secondary endpoint of B-35 was quality of life (QOL) and symptom (SX) outcomes in the two treatment groups. The primary hypotheses of the PRO study were that there would be no differences in QOL between the two treatments, and that patients receiving A would report higher rates of hot flashes compared to patients receiving tam. Other SX comparisons were secondary endpoints. Methods QOL and SX were assessed at baseline (prior to randomization), and every 6 months thereafter for 5 years of treatment and in the following 12 months. QOL was measured with the SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS). SX were measured with selected scales from the BCPT symptom-checklist, and other standardized instruments. Stratification was by age (&lt;60 v ≥60) as in the main trial. Study hypotheses and endpoints were examined by comparing PROs in the two treatment arms using a mixed model for repeated measures analysis with adjustment for the baseline scores, time point and age category, using an intention-to-treat principle and including only patients who completed the baseline and at least one follow-up questionnaire. Patients with protocol events were censored. Only data through 60 months are reported here. The accrual goal for the sub-study was 1,150 consecutive patients. Results Between January 6, 2003 and June 15, 2006, a total of 3,104 patients were entered and randomly assigned to NSABP Protocol B-35. Accrual to the PRO study of B-35 closed on December 28, 2004, at which time 1,275 patients were entered, with 1,193 patients included in this analysis. There were no medical or demographic differences between patients assigned to A or tam in the PRO sub-study, and they reflected the characteristics of the parent trial. Adherence to data collection across the 60 months was 87%. There were no significant differences in QOL outcomes by treatment for the PCS (p=0.16) or the MCS (p=0.38). SX subscales: hot flash scale was greater in tam group and this difference varied over time (p=0.001); musculoskeletal pain was significantly greater in A group for time points 6-24 months (all p&lt;.001); vaginal problems were greater in A group (p=0.03). Hot flash and vaginal problems were significantly worse in women &lt;60 years. Additional SX outcomes (depression, fatigue, sexual function) will be reported at presentation. Conclusion In this large, double-blind, placebo-controlled trial comparing A to tam in patients with DCIS, there was no significant difference in QOL between the two treatments. However, there were important treatment differences in SX outcomes, which should be considered as part of treatment decision-making discussions, along with the clinical breast cancer outcome results. Support: CA-180868, 180822, 189867, 196067, 114732; AstraZeneca Pharmaceuticals LP. Citation Format: Ganz PA, Cecchini RS, Julian TB, Margolese RG, Costantino JP, Vallow LA, Albain KS, Whitworth PW, Cianfrocca ME, Brufsky A, Gross HM, Soori GS, Hopkins JO, Fehrenbacher L, Sturtz K, Wozniak TF, Seay TE, Mamounas EP, Wolmark N. Patient-reported outcome (PRO) results, NRG Oncology/NSABP B-35: A clinical trial of anastrozole (A) vs tamoxifen (tam) in postmenopausal patients with DCIS undergoing lumpectomy plus radiotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S6-04.

Abstract Background: Ovarian carcinoma is composed of five major histologic types, which associate with outcome and predict therapeutic response. Our aim was to evaluate histologic type assessments across the centers participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model. Methods: Tissue microarrays (TMA) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histologic type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review. Results: The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of endometrioid carcinoma compared with HGSC became significant [RR 0.60; 95% confidence interval (CI), 0.37–0.93; P = 0.021], consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2. Conclusions: Research cohorts, particularly those across different centers within consortia, show significant variability in original histologic type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type. Impact: Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology. Cancer Epidemiol Biomarkers Prev; 22(10); 1677–86. ©2013 AACR.