The addition of trastuzumab (TH) to primary chemotherapy in HER2-positive breast cancer (BC) significantly improved pathological complete response (pCR) and survival. Concurrent use of TH to an anthracycline taxane-based regimen increased pCR but raised concerns about cardiac toxicity. Given the lower cardiotoxicity of liposomal doxorubicin hydrochloride (MYOCET®), the objective of this study was to explore the benefit of liposomal doxorubicin hydrochloride plus TH in a neoadjuvant scenario.
Patients with stage II-III HER2-positive BC were randomized to liposomal doxorubicin hydrochloride (60 mg/m2) plus cyclophosphamide (600 mg/m2) and TH (MCH) or conventional doxorubicin plus cyclophosphamide alone (AC), each followed by docetaxel (100 mg/m2) and TH. The primary objective of this trial, carried out in 21 European centers, was efficacy assessed by BC-pCR; secondary objectives included pCR by hormonal status and disease stage, progression-free survival (PFS) at 5 years, and safety.
From Mar 2008-Oct 2010, 126 patients were enrolled and were evaluable. No statistically significant differences were observed in demographics and baseline clinical characteristics between treatment groups. Adverse events and discontinuations during cycles 1-8 were similar in both treatment groups. pCR was 41.3% for the MCH group and 54.0% for the AC but differences were not statistically significant (p =.154, 95% CI −0.30 to 0.05). However, in patients with stage II disease, pCR was 31.0% vs 62.5% in favor of AC (p =.004; 95% CI 0.52-0.11). PFS was similar in both arms. The safety profile was similar in both groups; however, more patients in the AC group (12.7%) experienced cardiovascular events than in the MCH group (6.5%).
MCH was similar in efficacy to the traditional regimen of AC in terms of pCR in HER2-positive BC. However in stage II patients alone, the AC arm had a significant benefit in terms of pCR. More patients in the AC group experienced cardiovascular events than in the MCH group.
Clinical trial identification
Legal entity responsible for the study
This is a company-sponsored study: Teva Branded Pharmaceutical Products R&D, Inc. Sponsor's Responsible Medical Officer Richard Malamut, MD
Teva Branded Pharmaceutical Products R&D, Inc.
S. Paepke: Honoraria from Teva. All other authors have declared no conflicts of interest.