| General information |
| Database: | DB01072 |
| Objective: | Combination Chemotherapy and Paclitaxel Plus Trastuzumab in Treating Women With Palpable Breast Cancer That Can Be Removed by Surgery |
| Authors: | Aman U Buzdar |
| Title: | Fluorouracil, epirubicin, and cyclophosphamide (FEC75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC75 plus trastuzumab as neoadjuvant treatment for patients with human epidermal growth factor receptor 2positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. |
| Journal: | Lancet Oncology |
| Year: | 2013 |
| PMID: | 24239210 |
| Trial Design |
| Clinical Trial Id: | NCT00513292 |
| Agent: | Trastuzumab Emtansine
|
| Target: | human epidermal growth factor receptor 2 and microtubuleinhibitory
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Fluorouracil, epirubicin, and cyclophosphamide (FEC75) followed by paclitaxel plus trastuzumab |
| Study Type: | a randomised controlled trial, done in III6 centres in the USA and Puerto Rico. |
| Key Patients Feature: | aged 18 years or older who had a diagnosis of invasive breast cancer made by a core needle biopsy. Eligibility criteria were Eastern Cooperative Oncology Group performance status of 0 or 1; breast lesion of 2.0 cm or more or at least one positive lymph node biopsy sample; human epidermal growth factor receptor 2positive disease (3+ by immunohistochemistry or amplifi cation by fl uorescence insitu hybridisation); left ventricular ejection fraction (by multigated acquisition scan or, after protocol addendum number 4, by echocardiogram) 55% or more within 90 days of registration; and adequate blood chemistry results (absolute neutrophil count more than and equal to 1200 cell per ¦ÌL, platelet count more than and equal to 100 000 platelets per ¦ÌL, total bilirubin below institutional upper limit of normal, serum creatinine no greater than upper limit of normal, aspartate aminotransferase less than and equal to 1.5 ¡Á upper limit of normal, and alkaline phosphatase less than and equal to 2.5 ¡Á upper limit of normal). |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | NA |
| Control Group Info: | concurrent treatment |
| Treatment Info: | fluorouracil 500 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2 (FEC75) on day 1 of a 21day cycle for four cycles followed by paclitaxel 80 mg/m2 and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC75 (on day 1 of each 21day cycle) and onceweekly trastuzumab, in the same doses as the sequential group. Surgery, including evaluation of the axilla, was done within 6 weeks of completion of neoadjuvant treatment. |
| Primary End Point: | the percentage of patients who had a pathological complete response in the intentiontotreat population. |
| Secondary End Point: | NA |
| Patients Number: | 282 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 78 of 138 (56.5%, 95% CI 47.8-64.9) patients who received sequential treatment had a pathological complete response in the breast versus 77 of 142 (54.2%, 95% CI 45.7-62.6) who received concurrent treatment (diff erence 2.3%, 95% CI -9.3 to 13.9). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common severe toxic eff ects were neutropenia (35 [25.3%] of 138 patients in the sequential group vs 45 [31.7%] of 142 patients in the concurrent group) and fatigue (six [4.3%] vs 12 [8.5%]). Left ventricular ejection fraction dropped below the institutional lotheyr limit of normal at week 12 in one (0.8%) of 130 patients who received sequential treatment and four (2.9%) of 137 patients who received concurrent treatment; by week 24, it had dropped below this limit in nine (7.1%) of 126 patients and in six (4.6%) of 130 patients, respectively. |
| Conclusions: | Concurrent administration of trastuzumab with anthracyclines off ers no additional benefi t and is not warranted. |