Neoadjuvant Docetaxel and Capecitabine (TX) versus Docetaxel and Epirubicin (TE) for Locally Advanced or Early HER2-Negative Breast Cancer: An Open-Label, Randomized, Multi-Center, Phase II Trial

Abstract

PurposeThe Combination of taxanes and anthracyclines is still the mainstay of chemotherapy for early breast cancer. Capecitabine is an active drug with a favorable toxicity profile, showing strong anti-tumor activity against metastatic breast cancer. This trial assessed the efficacy and safety of the TX regimen (docetaxel and capecitabine) and compared it with the TE (docetaxel and epirubicin) regimen in locally advanced or high risk early HER2-negative breast cancer.Patients and MethodsThis randomized clinical trial was conducted at five academic centers in China. Eligible female patients were randomly assigned (1:1) to the TX (docetaxel 75mg/m2 d1 plus capecitabine 1000mg/m2 twice d1–14, q3w) or TE (docetaxel 75mg/m2 d1 plus epirubicin 75mg/m2 d1, q3w) groups for four cycles. The primary endpoint was a pathological complete response in the breast (pCR). Secondary endpoints included pCR in the breast and axilla, invasive disease-free survival (iDFS), overall survival (OS), and safety.ResultsBetween September 1, 2012, and December 31, 2018, 113 HER2-negative patients were randomly assigned to the study groups (TX: n = 54; TE: n = 59). In the primary endpoint analysis, 14 patients in the TX group achieved a pCR, and nine patients in the TE group achieved a pCR (25.9% vs. 15.3%), with a not significant difference of 10.6% (95% CI -6.0–27.3%; p = 0.241). In a subgroup with high Ki-67 score, TX increased the pCR rate by 24.2% (95% CI 2.2–46.1%; p = 0.029). At the end of the 69-month median follow-up period, both groups had equivalent invasive disease-free survival and overall survival rates. TX was associated with a higher incidence of hand-foot syndrome and less alopecia, with a manageable toxicity profile.ConclusionThe anthracycline-free TX regimen yielded comparable pCR and long-term survival rates to the TE regimen. Thus, this anthracycline-free regimen could be considered in selected patients.Trial RegistrationACTRN12613000206729 on 16/02/2013, retrospectively registered.