P3-14-13: A Prospective Open-Label Randomized Phase II Neoadjuvant Study of Non-Pegylated Liposomal Doxorubicin (MYOCET®) Plus Cyclophosphamide and Trastuzumab Versus Conventional Doxorubicin Plus Cyclophosphamide Alone, Each Followed by Docetaxel and Trastuzumab, in HER2−Positive Breast Cancer Patients.
Authors: Llombart-Cussac A , Pernas-Simon S , Rezai M , Hauschild M , Venturini M , Machiels J-P , Paepke S , Luporsi E , Kasiborski F , Kayitalire L 
Published: June 2012

Abstract
Background
The upfront addition of trastuzumab (Herceptin, H) to anthracycline/taxane-based primary chemotherapy significantly increases pathological complete response (pCR) in HER2−positive breast cancer (BC) patients (pts). However, concerns about the cardiac toxicity of concurrent administration of H and standard anthracyclines limited its use (Seidman et al 2002, J Clin Oncol 20:1215–21). MYOCET® (M) has a better cardiac tolerance profile than standard doxorubicin (Adriamycine, A) and might allow to give anthracyclines safely in combination with H. We explored the added benefit of early and longitudinal exposure to the combination of M with H in early-stage HER2−positive BC in a phase II multicentric randomized trial.
Methods: Women with stage II or IIIA HER2−positive BC were randomized to receive 4 cycles of either M + cyclophosphamide (C) + H (MCH) or AC every 3 weeks (q3w); then followed by 4 cycles of docetaxel + H (q3w). The primary endpoint was the pCR rate. Secondary endpoints included the overall and cardiac safety (using left ventricular ejection fraction [LVEF] and NYHA classification).
Results: Since September 2008, 126 pts with a median age of 51 and stage II (85 pts) or III (39 pts) BC were randomized: 1 pt did not initiate treatment, 12 discontinued treatment prematurely, 21 were still receiving treatment, 91 had completed treatment and 90 underwent surgery, as of January 15th 2011. Pathological responses are under central review.
In the MCH arm, 1 pt reported a NYHA class II cardiac event and 1 pt had asymptomatic LVEF decrease down to 42%. In the AC arm, 2 pts experienced NYHA class II events, 1 pt had LVEF value 17% below baseline, and 1 patient had LVEF value 6% below the lower normal limit. Mean (±SD) LVEF decrease from baseline to endpoint was 0.8% (±6.3) in the MCH arm and 3.8% (±5.8) in the AC arm.
Patients tended to report more grade 3 gastrointestinal (GI) adverse event in the MCH arm (8.1% of pts) than in the AC arm (4.8% of pts), mainly diarrhea (6.5% of pts in the MCH arm vs 1.6% in the AC arm). Other grade 3 GI toxicities were infrequent. Hematological toxicity was similar in both arms: 56.4% and 61.9% of pts developed grade 3/4 neutropenia, and 16.1% and 14.3% of pts reported febrile neutropenia, in the MCH and AC arms respectively. No severe case of palmar-plantar erythrodysaestheia syndrome was reported.
Conclusion: The concurrent administration of the non-pegylated liposomal doxorubicin MYOCET® and H has an acceptable early safety profile that should be confirmed with longer follow-up. Pathological response data are pending and will be presented at the meeting.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-13.