Abstract PD2-4: Subgroup efficacy analyses of the randomized phase III TANIA trial evaluating continued or reintroduced bevacizumab (BEV) after 1st-line BEV for HER2-negative locally recurrent/metastatic breast cancer (LR/mBC)
Authors: Puglisi Fabio , Cortes Javier , Vrdoljak Eduard , Gligorov Joseph , Marschner Norbert , Zielinski Christoph , de Laurentiis Michele , Brain Etienne , Lévy Christelle , Welt Anja , Kahan Zsuzsanna , Inbar Moshe , de Ducla Sabine , Freudensprung Ulrich , von Minckwitz Gunter 
Published: May 2015

Abstract
BACKGROUND: The open-label randomized phase III TANIA trial demonstrated statistically significantly improved progression-free survival (PFS; primary endpoint) with the addition of BEV to 2nd-line chemotherapy (CT) in patients (pts) with HER2-negative LR/mBC progressing after 1st-line BEV-containing therapy. We describe efficacy in clinically relevant subgroups to assess consistency of the BEV treatment effect.
METHODS: Pts whose HER2-negative LR/mBC had progressed during/after 1st-line BEV–CT were randomized 1:1 to investigator’s chosen 2nd-line single-agent CT given either alone or with BEV (15 mg/kg q3w or 10 mg/kg q2w). 2nd-line therapy was continued until disease progression (PD), unacceptable toxicity or consent withdrawal. At PD, BEV was continued with 3rd-line CT (investigator’s choice) in pts initially randomized to BEV–CT but was not permitted in pts randomized to CT alone. The primary endpoint was PFS from randomization to 2nd-line PD/death. Sample size was calculated based on a log-rank test assuming median PFS of 7→9.3 mo with a corresponding hazard ratio (HR) of 0.75. PFS events were required in 384 of 488 pts for 80% power at 2-sided α=0.05. Subgroup analyses of the primary endpoint were prespecified and included subgroups defined by stratification factors.
RESULTS: From Jan 2011 to Apr 2013, 494 pts were enrolled. The data cut-off for the primary analysis was Dec 20, 2013 (median follow-up: CT 15.9 mo; BEV–CT 16.1 mo). The PFS benefit seen in the overall population was observed consistently in most subgroups.
SubgroupPts with PFS events/Total No. of pts (%)Median 2nd-line PFS, moUnstratified HR (95% CI)CTBEV–CTCTBEV–CTAll203/247 (82)204/247 (83)4.26.30.75 (0.61-0.93)aHormone receptor statusbTriple negative56/60 (93)45/56 (80)2.14.90.59 (0.40-0.88)Positive, HER2 negative147/187 (79)159/191 (83)4.76.70.84 (0.67-1.05)1st-line PFS, mob&lt;661/69 (88)54/68 (79)3.95.10.62 (0.43-0.90)≥6142/178 (80)150/179 (84)4.66.40.82 (0.65-1.03)LDHb≤1.5×ULN167/207 (81)168/210 (80)4.46.30.77 (0.62-0.96)&gt;1.5×ULN36/40 (90)36/37 (97)2.15.80.73 (0.46-1.16)CT choicebTaxane25/32 (78)26/32 (81)3.26.90.55 (0.31-0.98)Non-taxane non-vinorelbine156/191 (82)151/188 (80)4.46.00.84 (0.68-1.06)Vinorelbine22/24 (92)27/27 (100)2.46.50.41 (0.22-0.75)CT choice (not stratified)Capecitabine117/146 (80)125/151 (83)4.96.20.92 (0.72-1.19)Non-capecitabine86/101 (85)79/96 (82)3.26.50.55 (0.40-0.75)BEV-free interval, wk≤6138/165 (84)130/149 (87)4.25.80.82 (0.64-1.04)&gt;665/81 (80)74/98 (76)4.47.60.72 (0.51-1.00)aStratified.bStratification factor.
CONCLUSIONS: PFS was statistically significantly improved with the addition of BEV to 2nd-line CT in BEV-pretreated pts, meeting the primary objective of TANIA. This effect was seen consistently within subgroups based on stratification factors. Within the limitations of exploratory subgroup analyses with small sample sizes, further subgroup analyses may suggest some potential inconsistencies in treatment effect. These hypothesis-generating observations require further exploration of potential differences in disease and pt characteristics in TANIA, which may have influenced physicians’ CT choice.
Citation Format: Fabio Puglisi, Javier Cortes, Eduard Vrdoljak, Joseph Gligorov, Norbert Marschner, Christoph Zielinski, Michele de Laurentiis, Etienne Brain, Christelle Lévy, Anja Welt, Zsuzsanna Kahan, Moshe Inbar, Sabine de Ducla, Ulrich Freudensprung, Gunter von Minckwitz. Subgroup efficacy analyses of the randomized phase III TANIA trial evaluating continued or reintroduced bevacizumab (BEV) after 1st-line BEV for HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD2-4.