262PD - Docetaxel + trastuzumab +/- non-pegylated liposomal doxorubicin +/- bevacizumab in the neoadjuvant treatment of early, HER2-positive breast cancer:...

Date 27 September 2014
Event ESMO 2014
Session Breast cancer, early stage
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Presenter Günther Steger
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors G.G. Steger1, R. Greil2, M. Hubalek3, M.A. Fridrik4, C. Singer5, R. Bartsch1, M. Balic6, P. Dubsky7, D. Egle3, S.P. Gampenrieder2, G. Pfeiler5, D. Mayr4, T. Czech3, G. Rinnerthaler2, A.L. Petzer8, P. Sevelda9, A. Lang10, S. Frantal11, M. Rudas12, M. Gnant13
  • 1Internal Medicine I/oncology, Medical University of Vienna, 1090 - Vienna/AT
  • 2Iiird Medical Department With Hematology And Oncology, Paracelsus Medical University, Salzburg/AT
  • 3Department Obstetrics And Gynecology, University Hospital Innsbruck, 6020 - Innsbruck/AT
  • 4Internal Medicine 3, Allgemeines Krankenhaus Linz, AT-4020 - Linz/AT
  • 5Gynaecology, Medical University of Vienna, 1090 - Vienna/AT
  • 6Department Of Internal Medicine/oncology, Medical University of Graz, Graz/AT
  • 7Surgery, Medical University of Vienna, 1090 - Vienna/AT
  • 8Interne I:hematology And Oncology, Krankenhaus der Barmherzigen Schwestern, AT-4040 - Linz/AT
  • 9Gynaecology, Hietzing Hospital, Vienna/AT
  • 10Internal Medicine, Feldkirch Hospital, Feldkirch/AT
  • 11Statistics, Austrian Breast and COlorectal Cancer Study Group, Vienna/AT
  • 12Pathology, Medical University of Vienna, 1090 - Vienna/AT
  • 13Deparment Of Surgery, Medical University of Vienna, 1090 - Vienna/AT

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 <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 (DH) vs. 44% in each of the experimental groups (power: 80%, two-sided alpha: 0.05).

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.