Nine-Year Median Follow-up of Cardiotoxicity and Efficacy of Trastuzumab Concurrently With Anthracycline-Based and Anthracycline-Free Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer Patients

Background: The combination of trastuzumab with anthracycline chemotherapy drugs is associated with synergistic cardiotoxicity. The aim of this study is to compare the efficacy and late-onset cardiac toxicity of neoadjuvant chemotherapy regimens, trastuzumab plus paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide (PH-FECH) versus trastuzumab plus docetaxel and carboplatin (TCH), for human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). Methods: Patients with HER2+ BC who received neoadjuvant chemotherapy with PH-FECH or TCH between 2002 and 2009 at MD Anderson Cancer Center were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints included pathological complete response (pCR), overall survival, cardiac events, breast cancer-specific survival, noncardiac toxicities, and chemotherapy interruption. Results: We identified 249 consecutive patients (184 who received PH-FECH and 65 who received TCH). The 10-year PFS was higher in the PH-FECH group than in the TCH group (83.6% vs. 72.2%; P =.044). The pCR rate was significantly higher in the PH-FECH group (58.2% vs. 41.5%; P =.021). The rate of cardiac events was higher in the PH-FECH group, but the difference was not significant (13.0% vs. 7.7%; P =.352). More patients developed late-onset cardiotoxicity in the PH-FECH group (3.8%) than in the TCH group (1.5%). Hypertension (odds ratio, 4.402 [95% confidence interval, 1.020-18.998]; P =.047) was an independent predictor of late-onset cardiotoxicity. Conclusions: Both neoadjuvant regimens are effective and tolerable in patients with HER2+ BC. The PH-FECH regimen offers a higher pCR rate and higher PFS but no difference in overall survival or breast cancer-specific survival. Higher frequency of cardiac toxicity with PH-FECH was noted. (C) 2021 Elsevier Inc. All rights reserved.