Arimidex/Faslodex/Iressa Study: A Phase II Trial of Primary Systemic Therapy Using a Combination of Arimidex, Faslodex and Iressa (Gefitinib) in Postmenopausal Women With Hormone Receptor Positive Breast Cancer
Over the last three decades, a steady shift has occurred in the management of breast cancer.
Because it was traditionally viewed as a local disease, many advocated the use of radical
surgery to achieve maximum survival benefit. This view has been slowly replaced by a broader
biologic view that recognizes the often systemic nature of breast cancer, even when it
appears to be localized to the breast. Results from randomized clinical trials have
demonstrated that less extensive surgery or lumpectomy plus radiation therapy are optimal
for local management of early breast cancer. In addition to the less radical approach to
surgical treatment of breast cancer, other randomized clinical trials established the value
of postoperative (adjuvant) systemic therapy in improving overall survival by eradicating
micrometastatic disease, the major cause of mortality from breast cancer. An improved
survival has been shown from using chemotherapy as well as the antiestrogen tamoxifen in the
adjuvant setting and has been confirmed through the overview analyses from the Early Breast
Cancer Trialist Collaborative Group. Despite the well-documented benefits of adjuvant
systemic therapy, it is not effective in preventing death from breast cancer in all patients
who are candidates for such treatment. The worth of such therapy can only be judged in
retrospect upon disease relapse, a time when breast cancer is nearly always incurable.
Currently, there are few reliable methods to predict the success or failure of a particular
postoperative treatment modality and better ways to predict and optimize outcome are needed.
Preoperative (primary, neoadjuvant) systemic therapy is an alternative approach that is
based on a strong rationale. With the tumor still in place and directly accessible, this
form of therapy allows direct observation of response to treatment which may predict the
likelihood of controlling distant micrometastatic disease and also enables the sampling of
tissue to explore molecular correlates of response and also the mechanisms of action of
therapeutic agents. Furthermore, it allows early identification of patients with refractory
disease who might benefit from alternative treatments before they develop macrometastatic
disease and miss the opportunity for a cure. Primary systemic therapy can also help
facilitate surgery and debulking of disease in those patients with initially inoperable
tumors, as well as improve the odds of breast conservation.
A pivotal trial that established the role of preoperative systemic therapy was the NSABP
trial B-187. In this trial, women with localized breast cancer were randomized to receive
Adriamycin, Cytoxan (AC) either preoperatively or postoperatively. There was no difference
between the two groups in disease-free and overall survival. Furthermore, quantifying tumor
response preoperatively allowed prediction of patient outcome in terms of disease-free and
overall survival. Specifically, patients achieving a pathologic complete response, i.e.,
complete disappearance of invasive cancer on pathologic examination, had the best outcome,
establishing the role of response as a valid surrogate predictor of the sensitivity of
distant micrometastatic disease to chemotherapy and subsequent clinical outcome. In
addition, breast-conserving surgery was more frequently performed in the preoperative
treatment group, an advantage over the postoperative treatment approach. Most importantly,
however, NSABP trial B-18 showed conclusively that primary systemic therapy is safe and does
not place patients at a disadvantage by delaying primary surgical treatment. Another large,
multicenter prospective trial conducted by the European Organization for Research and
Treatment of Cancer (EORTC) confirmed the findings of NSABP trial B-18.
Primary study objective:
- To determine the clinical response rate of primary breast cancer to the combination of
Arimidex, Faslodex, and Iressa
Secondary study objectives:
- To study molecular changes in response to treatment
- To determine the pathologic response rate
- To assess the tolerability and safety of the combination regimen
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary study objective - To determine the clinical response rate of primary breast cancer to the combination of Arimidex, Faslodex, and Iressa
until disdase progression
Yes
Mothaffar Rimawi, MD
Principal Investigator
Baylor Breast Center
United States: Food and Drug Administration
H-14732
NCT00206414
January 2003
September 2006
Name | Location |
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Baylor Breast Center | Houston, Texas 77030 |