262PD - Docetaxel + Trastuzumab +/- Non-Pegylated Liposomal Doxorubicin +/- Bevacizumab in the Neoadjuvant Treatment of Early, Her2-Positive Breast Cancer: First Results of Abcsg-32

Abstract

ABSTRACT Aim: ABCSG-32 was designed to evaluate the cardiac toxicity of bevacizumab (B) and non-pegylated liposomal doxorubicin (N) when added to docetaxel + trastuzumab (DH) in the neoadjuvant treatment of early, HER2-positive breast cancer (BC) within a randomized phase II trial. Secondary aims were to evaluate the non-cardiac safety and the efficacy of the 4 drug combinations as measured by the rates of pathological complete responses (pCR). Methods: 100 patients (pts) with biopsy-proven, invasive, early, HER2-pos breast cancer were stratified according to major risk factors including estrogen-receptor-status, histology, grading, and center and were randomized to receive 6 cycles (q 21 days) of either D100 mg/m2 + H8/6 mg/kg (DH, n = 25), DH + B15 mg/kg (DHB, n = 25), D75H + N 50 mg/m2 (DHN, n = 26), or D75HN + B 15 mg/m2 (DHNB, n = 24). All pts received pegfilgrastim 6 mg sc on day 2. 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-IV, or an asymptomatic drop of EF (adEF) of >15% from baseline, or an adEF Results: Cardiac toxicity was low with a CTE in only 3 pts (DH: 0, DHB: 1, DHN: 1, DHNB: 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: DH: 8, DHB: 12, DHN: 14, DHNB: 16; SSE: DH: 23, DHB: 31, DHN: 29, DHNB: 31). No differences in the incidence of non-serious AE and no new safety signals for B and N were detected. In 8 pts the treatment was terminated early (DH: 0, DHB: 3,DHN: 2, DHNB: 3). The overall rate of pCR was 52% (DH: 36%, DHB: 50%, DHN: 63%, DHNB: 62%). Conclusions: Our data show that neoadjuvant DH, DHB, DHN, and DHNB can be safely administered to pts with HER2-positive early BC. Cardiac toxicity is low when 6 cycles are given and non-cardiac toxicity is acceptable but higher during the 3/4-drug combinations leading to the early termination of treatment in some patients. All regimens tested are highly effective with pCR-rates >60% after DHN and DHNB. Disclosure: G.G. Steger: Reseach grants, travel grants, advisory boards, and honoraria from Hoffmann La Roche, Roche Austria, Cephalon, TEVA/Ratiopharm, and Amgen; R. Greil: Research Support and advisory boards from Roche, Amgen, Ratiopharm/Teva, Cephalon; M. Hubalek, M.A. Fridrik, C. Singer, M. Balic, P. Dubsky, D. Mayr, P. Sevelda, A. Lang and S. Frantal: Research grants from Roche Austria, Cephalon, TEVA/Ratiopharm, Amgen; R. Bartsch: Research grants, lecture honoraria, travel support from Roche Austria, lecture honoraria Teva/Ratiopharm; D. Egle: Travel grants and honoraria from Roche Austria and TEVA/Ratiopharm; S.P. Gampenrieder: Research Support and travel Support from Roche and Amgen; G. Pfeiler: Honoraria and travel grants from Novartis, Amgen, Roche Austria; T. Czech: Travel Support from Roche Austria; G. Rinnerthaler: Research Support and travel Support from Roche and Amgen; A.L. Petzer: Research grants from Roche Austria, Cephalon, TEVA/Ratiopharm, Amgen, advisory boards and honoraria from Roche Austria, M. Gnant: Research and travel grants, advisory boards and honoraria from Roche Austria, Cephalon, TEVA/Ratiopharm, Amgen. All other authors have declared no conflicts of interest.