Phase II study of liposome-encapsulated doxorubicin plus cyclophosphamide, followed by sequential trastuzumab plus docetaxel as primary systemic therapy for breast cancer patients with HER2 overexpression or amplification

Breast. 2013 Dec;22(6):1101-7. doi: 10.1016/j.breast.2013.09.001. Epub 2013 Sep 26.

Abstract

Purpose of the study: Trastuzumab combined with sequential chemotherapy with taxanes and anthracyclines as primary systemic therapy achieved high rates of pathologic complete response (pCR). Non-pegylated liposome-encapsulated doxorubicin (NPLD) has shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab with sequential chemotherapy for early or locally advanced HER2 positive BC.

Methods: Preoperative treatment included NPLD (60 mg/mq iv) plus cyclophosphamide (600 mg/mq iv) every 3 weeks for 4 cycles followed by docetaxel (35 mg/mq iv) plus trastuzumab (4 mg/mq loading dose iv, then 2 mg/mq iv) weekly for 16 weeks. Primary endpoint was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Clinical staging was exploratory evaluated by CT-PET.

Results: 43 pts were treated from december 2005 to September 2011, 39 of them were evaluable for the purpose of study. Median age was 53 years (range: 31-78), the majority of pts had tumour stage cT2 (63%), tumour grade 3 (86%), clinical nodes involvement N+ (77%), ER positive (56%) and Ki-67 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. There was an association between Ki-67 ≥20% at baseline and pCR (p = 0.018). No cardiac toxicity or discontinuation of trastuzumab was reported. CT-PET modified the clinical stage for 10 patients showing new loco-regional lymph nodes.

Conclusions: This study confirms that integrating anti-HER2 therapy in primary treatment for HER2 positive breast cancer is active. NPLD is a safe option to minimize cardiotoxicity.

Keywords: Breast cancer; HER-2 positive; Liposomal anthracycline; Neoadjuvant chemotherapy; Pathologic complete response; Trastuzumab.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Carcinoma / blood
  • Carcinoma / drug therapy*
  • Carcinoma / pathology*
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Polyethylene Glycols / administration & dosage
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Receptor, ErbB-2 / blood*
  • Taxoids / administration & dosage
  • Tomography, X-Ray Computed
  • Trastuzumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Radiopharmaceuticals
  • Taxoids
  • liposomal doxorubicin
  • Fluorodeoxyglucose F18
  • Docetaxel
  • Polyethylene Glycols
  • Doxorubicin
  • Cyclophosphamide
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab