Additional strategies for resistant HER2+, ER+

[Tom]

Resistant HER-2-positive breast cancer may respond to fulvestrant

Martha Kerr
Reuters Health
Posting Date: December 15, 2006

Last Updated: 2006-12-15 16:49:09 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Fulvestrant (Faslodex, AstraZeneca, London) shows efficacy and tolerability in women with advanced HER-2-positive breast cancer that has failed to respond to nonsteroidal aromatase inhibitor therapy.

The phase III results of the EFECT trial, a randomized, multicenter study of that compared the efficacy of fulvestrant with exemestane (Aromasin, Pfizer Oncology, New York) in 693 women with hormone receptor-positive advanced breast cancer who had failed aromatase therapy, were announced here at the 29th annual San Antonio Breast Cancer Symposium.

The fulvestrant protocol contained a loading dose phase, with 500 mg IM on day 0 and 250 mg IM on days 14 and 28, followed by 250 mg IM every 28 days. The exemestane arm consisted of 25 mg per day, orally. Treatment continued until disease progression, death or withdrawal from the study.

Approximately 60% of patients had visceral metastases and approximately 60% had already received two or more courses of endocrine therapy.

Principal investigator Dr. William Gradishar of Northwestern University in Chicago reported that disease progression occurred in 82.1% of patients on fulvestrant and in 87.4% of those on exemestane, with a median time to disease progression of 3.7 months in both groups. Clinical benefit was approximately 32% in both groups. Both treatments were well-tolerated.

"This is the only randomized trial to address the optimal sequence of treatment in metastatic breast cancer resistant to first-line treatment," Dr. Gradishar told Reuters Health prior to his presentation of the EFECT trial results Friday.

"We used a loading dose (of fulvestrant) in order to reach a steady state quickly," Dr. Gradishar commented.

"The bottom line is that after disease progression with nonsteroidal aromatase inhibitor therapy, fulvestrant and exemestane are comparable treatment options."

"You always want to individualize treatment, but when there are issues with compliance with therapy or difficulty with taking pills, you may want to choose fulvestrant because it is injectable...Otherwise, there is no reason to choose one over the other according to patient subset."

[heblaj01]

A potentially more important Phase 2 clinical of Fulvestrant+ Herceptin is running since April 2006 under Dr Pietras. It is unfortunately going slow due to low enrolment of patients.
If the theory backing the trial is confirmed it would prove that Fulvestrant in suppressing the estrogen receptors (without affecting estrogen) prevents interaction between the ER & HER-2 which is said to occur at least in some cases when Herceptin treatment leads to activation of the ER pathway independantly of circulating estrogen.