Abstract P3-11-06: Bevacizumab in combination with docetaxel+trastuzumab +/- non-pegylated liposomal doxorubicin: Final results of ABCSG-32, a prospective, randomized phase II-study
Authors: Steger Guenther G , Greil Richard , Hubalek Michael , Fridrik Michael A , Singer Christian F , Bartsch Rupert , Balic Marija , Dubsky Peter , Egle Daniel , Gampenrieder Simon P , Pfeiler Georg , Mayr David , Czech Theresa , Rinnerthaler Gabriel , Exner Ruth , Petzer Andreas L , Sevelda Paul , Lang Alois , Rudas Margaretha , Krause Barbara , Seifert Michael , Frantal Sophie , Zielinski Christoph C , Gnant Michael 
Published: May 2015

Abstract
BACKGROUND
Pathological complete response (pCR) after neoadjuvant systemic therapy is correlated with better prognosis in HER2-positive, early breast cancer. Bevacizumab (B) was shown to add efficacy to neoadjuvant systemic treatment in HER2-negative, early breast cancer in terms of pCR-rate but failed in the adjuvant setting of both, HER2-negative and HER2-positive disease. The role of B in the neoadjuvant treatment of HER2-positive, early breast cancer is not defined. Thus, ABCSG-32 was designed as a randomized phase II trial to evaluate the efficacy, the non-cardiac safety, and the cardiac toxicity of B when added to docetaxel + trastuzumab (DT) +/- non-pegylated liposomal doxorubicin (N) in the neoadjuvant setting of early, HER2-positive breast cancer.
METHODS
100 patients with biopsy-proven, invasive, early, HER2-positive breast cancer were stratified according to major risk factors including estrogen receptor (ER)-status, histology, tumor grade, and center and were randomized to receive 6 cycles (q 21 days) of either D100 mg/m2+T8/6mg/kg (DT, n=25), DT+B15mg/kg (DTB, n=25), D75T+N50 mg/m2 (DTN, n=26), or D75TN+B15 mg/m2 (DTNB, n=24). All patients received pegfilgrastim 6 mg sc on day 2. pCR was defined as the absence of invasive tumor cells in the breast and total pCR (tpCR) was defined as the absence of invasive tumor cells in the breast and axillary nodes after NST. Left ventricular (LV) ejection fraction (EF) was measured at baseline, before each treatment cycle, and before sugery. A cardiac
toxicity event (CTE) was defined as the occurrence of either symptomatic LV dysfunction NYHA II-III, or an asymptomatic drop of EF (adEF) of &gt;15% from baseline, or an adEF &lt;50%, or the appearance of significant arrhythmias requiring treatment. The trial was designed to detect a difference in the incidence of CTE of 8% in the control group (DT) vs. 44% in each of the experimental groups (power: 80%, two-sided alpha: 0.05).
RESULTS
The overall rate of pCR in all patients was 52% (DT: 36%, DTB: 51%, DTN: 63%, DTNB: 62%). In the ER-negative subgroup (n=43) the overall pCR rate was 63% (DT: 31%, DTB: 70%, DTN: 75%, DTNB: 88%) and the overall tpCR rate was 60% (DT: 31%, DTB: 60%, DTN: 75%, DTNB: 88%). Cardiac toxicity was low with a CTE in only3 patients (DT:0, DHB:1, DTN:1, DTNB:1). Non-cardiac toxicity/patient as evaluated by the incidence of serious adverse events (SAE,n=50) and significant safety events (SSE, n=114) was acceptable (SAE: DT:8, DTB:12, DTN:14, DTNB: 16; SSE: DT: 23, DTB: 31, DTN: 29, DTNB: 31). No differences in the incidence of non-serious AE and no new safety signals for B and N were detected. In 8 patients the treatment was terminated early (DT: 0, DTB: 3, DTN: 2, DTNB: 3).
CONCLUSIONS
Our data show that all regimens tested are effective in inducing pCR in HER2-positive early breast cancer. The addition of B and/or N to DT may lead to pCR/tpCR-rates of 51-88% with the highest activity seen in the ER-negative subgroup. 6 cycles of these regimens can safely be administered to patients with HER2-positive early breast cancer and further phase III-evaluation appear to be warranted.
Citation Format: Guenther G Steger, Richard Greil, Michael Hubalek, Michael A Fridrik, Christian F Singer, Rupert Bartsch, Marija Balic, Peter Dubsky, Daniel Egle, Simon P Gampenrieder, Georg Pfeiler, David Mayr, Theresa Czech, Gabriel Rinnerthaler, Ruth Exner, Andreas L Petzer, Paul Sevelda, Alois Lang, Margaretha Rudas, Barbara Krause, Michael Seifert, Sophie Frantal, Christoph C Zielinski, Michael Gnant. Bevacizumab in combination with docetaxel+trastuzumab +/- non-pegylated liposomal doxorubicin: Final results of ABCSG-32, a prospective, randomized phase II-study [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 P3-11-06.