Multicenter study of primary systemic therapy with docetaxel, cyclophosphamide and trastuzumab for HER2-positive operable breast cancer: the JBCRG-10 study

• Published in: Japanese journal of clinical oncology Vol. 50; no. 1; pp. 3 - 11
• Main Authors: Ueno, Takayuki, Masuda, Norikazu, Sato, Nobuaki, Ohtani, Shoichiro, Yamamura, Jun, Matsunami, Nobuki, Kashiwaba, Masahiro, Takano, Toshimi, Takahashi, Masato, Kaneko, Koji, Ohno, Shinji, Morita, Satoshi, Toi, Masakazu
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 24.01.2020
• Subjects: Adult; Aged; Anthracyclines - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Disease-Free Survival; Docetaxel - adverse effects; Docetaxel - therapeutic use; Epirubicin - therapeutic use; Female; Fluorouracil - therapeutic use; Humans; Middle Aged; Neoadjuvant Therapy - methods; Original; Receptor, ErbB-2 - metabolism; Taxoids - therapeutic use; Trastuzumab - adverse effects; Trastuzumab - therapeutic use; Young Adult; TCH (docetaxel, cyclophosphamide and trastuzumab); non-anthracycline regimen; HER2-positive breast cancer; primary systemic therapy; LVEF (left ventricular ejection fraction)
• ISSN: 1465-3621; 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyz119

Abstract Background The original aim of this study was to evaluate the treatment sequence and anthracycline requirement in docetaxel, cyclophosphamide and trastuzumab therapy. After one death in the anthracycline-containing arm, the protocol was amended to terminate the randomization. The single-docetaxel, cyclophosphamide and trastuzumab arm was continued to examine the efficacy and safety of the anthracycline-free regimen. Methods Women with human epidermal growth factor receptor-2-positive, operable and primary breast cancer were randomized to receive 5-fluorouracil, epirubicin and cyclophosphamide (four cycles) followed by docetaxel, cyclophosphamide and trastuzumab (four cycles), or docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide, or docetaxel, cyclophosphamide and trastuzumab (six cycles). After the protocol amendment, patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm alone. The primary endpoint was a pathological complete response. Results In total, 103 patients were enrolled between September 2009 and September 2011: 21, 22 and 24 patients in the 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel, cyclophosphamide and trastuzumab; docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide and docetaxel, cyclophosphamide and trastuzumab arms, respectively, and 36 patients in the docetaxel, cyclophosphamide and trastuzumab arm after the protocol amendment. In total, 60 patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm, in which the pathological complete response rate was 45.8%, and disease-free survival at 3 years was 96.6%. Patients with stage I or IIA in the docetaxel, cyclophosphamide and trastuzumab arm showed good disease-free survival (100% at 3 years). The comparison of efficacy among the three arms was statistically underpowered. Left ventricular ejection fraction decreased significantly after 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel–docetaxel, cyclophosphamide and trastuzumab (P = 0.017), but not after docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide or docetaxel, cyclophosphamide and trastuzumab. Conclusions The pathological complete response rate for docetaxel, cyclophosphamide and trastuzumab was similar to previous reports of anthracycline-containing regimens. Docetaxel, cyclophosphamide and trastuzumab might be an option for primary systemic therapy in human epidermal growth factor receptor-2-positive early breast cancer. A larger confirmatory study is necessary. Neoadjuvant docetaxel, cyclophosphamide and trastuzumab provided a pathological complete response rate of 45.8% and 3-year disease-free survival of 96.6%, comparable to those of reported anthracycline-containing regimens. Docetaxel, cyclophosphamide and trastuzumab might be an option for human epidermal growth factor receptor-2-positive breast cancer.