Abstract CT322: Efficacy of first-line capecitabine (CAP) ± bevacizumab (BEV) according to risk factors in the RIBBON-1 randomized phase III trial in locally recurrent/metastatic breast cancer (LR/mBC)
Authors: Robert Nicholas J. , Dieras Veronique , Jackisch Christian , Srock Stefanie , Freudensprung Ulrich , Faoro Leonardo , O’Shaughnessy Joyce 
Published: May 2015

Abstract
BACKGROUND: Analysis of data from 2203 patients (pts) with HER2-negative LR/mBC treated in the single-arm ATHENA study suggested that overall survival (OS) expectancy of a well-defined subset of pts with hormone receptor-positive LR/mBC was similar to that of pts with triple-negative breast cancer (TNBC). We used prognostic factors from ATHENA to analyze efficacy in the CAP cohort of the RIBBON-1 trial.
PATIENTS AND METHODS: In the CAP cohort of RIBBON-1, pts with LR/mBC were randomized 2:1 to receive CAP with either BEV 15 mg/kg q3w (N=409) or placebo (PLA; N=206). The primary endpoint was investigator-assessed progression-free survival (PFS). Objective response rate (ORR) and 1-year OS rate were secondary endpoints. Exploratory efficacy analyses were done in three subgroups: TNBC; high-risk hormone receptor positive (&gt;2 risk factors); and low-risk hormone receptor positive (≤2 risk factors) using the remaining risk factors identified in ATHENA (liver metastases/≥3 involved organs; disease-free interval [DFI] ≤24 months; prior anthracycline/taxane). The data cut-off was July 31, 2008.
RESULTS: In all three subgroups, PFS and ORR numerically favored BEV-CAP, consistent with the significant PFS and ORR benefit in the intent-to-treat population. Median PFS, median OS, and 1-year OS rate with PLA-CAP suggested a similarly poor prognosis in pts with TNBC and pts with high-risk hormone receptor-positive LR/mBC.
CONCLUSIONS: In these exploratory analyses, median OS in pts with high-risk hormone receptor-positive LR/mBC was short and similar to that in pts with TNBC, as seen in the ATHENA exploratory analysis.
OutcomePLA-CAPBEV-CAPTNBCN=50N=87PFS events, n (%)42 (84)74 (85)PFS unstratified HR (95% CI)0.72 (0.49-1.06)Median PFS, months (95% CI)4.2 (3.5-5.9)6.1 (4.3-8.2)ORR, % (95% CI)10.6 (3.5-23.1)30.3 (20.2-41.9)1-year OS rate, % (95% CI)71 (55-81)70 (59-79)Deaths, n (%)26 (52)47 (54)Median OS, months (95% CI)20.5 (15.8-NR)19.7 (14.6-23.2)Hormone receptor-positive disease with additional risk factors*N=56N=92PFS events, n (%)42 (75)72 (78)PFS unstratified HR (95% CI)0.80 (0.54-1.17)Median PFS, months (95% CI)4.4 (3.1-6.2)7.1 (4.3-8.6)ORR, % (95% CI)22.4 (11.8-36.6)27.7 (18.4-38.6)1-year OS rate, % (95% CI)66 (52-77)80 (70-87)Deaths, n (%)32 (57)52 (57)Median OS, months (95% CI)19.6 (12.9-23.4)20.8 (17.5-25.7)Hormone receptor-positive disease with limited additional risk factors**N=90N=220PFS events, n (%)68 (76)139 (63)PFS unstratified HR (95% CI)0.67 (0.50-0.89)Median PFS, months (95% CI)7.7 (6.0-8.4)10.6 (9.1-12.0)ORR, % (95% CI)36.8 (24.4-50.7)41.5 (33.8-49.6)1-year OS rate, %86 (77-92)85 (80-89)Deaths, n (%)34 (38)83 (38)Median OS, months (95% CI)28.4 (23.4-NR)29.0 (25.8-NR)*ER and/or PgR positive with &gt;2 risk factors (liver metastases/≥3 involved organs; DFI ≤24 months; prior anthracycline/taxane); **ER and/or PgR positive with ≤2 risk factors.
Citation Format: Nicholas J. Robert, Veronique Dieras, Christian Jackisch, Stefanie Srock, Ulrich Freudensprung, Leonardo Faoro, Joyce O’Shaughnessy. Efficacy of first-line capecitabine (CAP) ± bevacizumab (BEV) according to risk factors in the RIBBON-1 randomized phase III trial in locally recurrent/metastatic breast cancer (LR/mBC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT322. doi:10.1158/1538-7445.AM2014-CT322