Source: Rev Assoc Med Bras  |  Posted 6 years ago

Trial Halted Early Due to Lack of Response

By Cameron Johnston

SAN ANTONIO, TX -- December 13, 2005 -- Hormone-resistant breast cancers do not appear to respond to treatment with Iressa (gefitinib), according to results of an Australian-New Zealand study presented here.

In fact, the negative findings from the study were conclusive enough that enrollment in the trial was halted early and no further investigation into this area of study is planned.

Prue Francis, MD, study leader, Australian-New Zealand Breast Cancer Trials Group, and medical oncologist, Peter McCallum Cancer Centre, Melbourne, Australia, presented the data from this study here on December 10[^]th[] at the 28[^]th[] Annual San Antonio Breast Cancer Symposium (SABCS).

The current thinking is that there is an inverse relationship between estrogen receptor and epidermal growth factor receptor (EGFR) expression. The theory goes that cancer cells that are estrogen receptor-negative are more likely to express higher levels of EGFR and could potentially respond to anti-EGFR therapy. Cancer cells that were hormone receptor-positive generally had lower levels of EGFR, except in cases where they developed resistance to hormonal therapy -- then they too had an increased expression of EGFR.

To assess the efficacy and safety of single agent gefitinib 500 mg once daily in 2 separate parallel groups of advanced breast cancer patients, Dr. Francis and colleagues enrolled 1 group of 39 women whose breast cancer had progressed despite hormonal therapy (ie, they developed a resistance to the therapy) and a second group of 27 women who did not overexpress either the estrogen or progesterone receptors.

The women, all with advanced disease, were treated with 500 mg/day of Iressa and were assessed at 8-week intervals. Clinical benefit was defined as complete, partial, or stable response for at least 24 weeks.

There were no complete or partial responses and the mean time to progression in both groups was 8 weeks. Two patients in the hormone receptor-negative group showed signs of stable disease, for a clinical benefit rate of 7.7%. One of these had progression after 40 weeks, the other ceased gefitinib therapy due to adverse effects and switched treatments.

Tumor samples for 47 of the 66 women enrolled were tested for EGFR expression to determine whether there was a correlation expression and disease control, but the numbers were too small to produce any useful data, Dr. Francis said. Enrollment in the trial was discontinued due to the less than favorable results, he said.

This trial illustrates the fact that what happens in the preclinical setting does not always come to pass in clinical trials, the authors noted. It had been shown in previous laboratory studies that the EGFR inhibitor was more active against hormone receptor-positive tumors that had developed a resistance to hormonal treatments, but that was not the case in this study.

The women in this study were treated with a dose that was double the dose used in the treatment of non-small-cell lung cancer.

[Presentation title: Gefitinib Has a Low Clinical Benefit Rate in Advanced Breast Cancer Patients. Abstract 4080]