SAN FRANCISCOIn a multicenter phase II trial reported at the 37th
Annual Meeting of the American Society of Clinical Oncology (ASCO abstract
178), the new selective estrogen-receptor modulator (SERM) arzoxifene showed
antitumor efficacy without endometrial hyperplasia in 112 patients with
advanced or metastatic breast cancer.
The lead author was Aman Buzdar, MD, professor of breast medical oncology,
M.D. Anderson Cancer Center.
Arzoxifene has been shown to be antagonistic in preclinical breast and
endometrial models while agonistic on bone and lipids. This phase II trial
evaluated the safety, toxicity, and efficacy of two dose levels (20 mg and 50
mg daily) of arzoxifene.
Patients had either tamoxifen (Nolvadex)-sensitive disease (no prior
systemic therapy or disease-free interval of at least 12 months after
discontinuation of adjuvant tamoxifen) or tamoxifen-refractory disease (relapse
on adjuvant tamoxifen or relapse on tamoxifen for first-line treatment of
The arms were balanced for tamoxifen sensitivity, degree of
estrogen-receptor positivity, and number of metastatic sites. Patients were
randomized in a double-blind design to 20 mg or 50 mg daily. Patients who
progressed were given 50 mg daily or went off study.
"There are unmet needs with tam-oxifen, which is the SERM
standard," said Allen S. MeLemed, MD, clinical research physician for
Lilly Research Laboratories, which is developing the drug. "Particularly,
there are concerns about endometrial cancer and hyperplasia. We want to see if
this compound is a better SERM. Arzoxifene seems to have better preclinical
efficacy than raloxifene [Evista], which is why we took this phase II study
Both doses showed efficacy. The combined objective response rate for
protocol-qualified patients in the tamoxifen-sensitive cohort was 19%, with a
clinical benefit seen in 40% (complete response plus partial response plus
stable disease). In the tamoxifen-refractory patients, the objective response
rate was 9%, and clinical benefit rate was 12%.