BARCELONAPreliminary results of a trial of a new selective
estrogen-receptor modulator (SERM), known as LY353381, show a 32%
response rate in patients with previously untreated locally advanced
or metastatic breast cancer, José Baselga, MD, of Vall
dHebron University Hospital, Barcelona, Spain, said at the San
Antonio Breast Cancer Symposium.
LY353381 acts as a potent estrogen antagonist in the breast and
in the uterus, Dr. Baselga said, while acting as an
estrogen agonist to maintain bone density and lower cholesterol levels.
A phase I trial examining four dose levels (10, 20, 50, and 100 mg
per day) found no dose-limiting toxicities, he said. The primary
objective of the phase II trial, Dr. Baselga said, was to
select whether 20 mg or 50 mg was the best daily dose of LY353381, as
reflected by tumor response rate or clinical benefit rate.
The Phase II Trial
The phase II trial, conducted at several facilities in Spain, France,
Belgium, and the Czech Republic, included 92 patients randomized to
receive, in a double-blind fashion, 20 mg or 50 mg daily of LY353381.
Dr. Baselga noted that patients initially placed on 20 mg could be
elevated to 50 mg upon progression at the discretion of the
investigator. Interim data were available on 87 patients, with a
median age of 70 (range, 37 to 94).
The time from diagnosis to inclusion in the study was fairly rapid,
he noted, at about 1 month. A significant proportion of patients had
either skin/soft tissue sites of metastasis or node-only disease (40
patients) as opposed to visceral and bone metastases (47 patients).
Eligibility criteria included pathologic confirmation of locally
advanced breast cancer (31 patients) or metastatic breast cancer (56
patients); ER- positive and/or PR-positive disease (although patients
older than 50 were admitted with unknown ER or PR status); and no
prior systemic therapy for locally advanced or metastatic breast
Patients who had received adjuvant therapy were admitted if they had
completed chemotherapy 6 months or more prior to metastatic disease,
or had received tamoxifen (Nolvadex) 12 months or more prior to
admission to the study. He noted that the majority of patients had
not received prior tamoxifen.
The overall response rate in all patients with a median time on
therapy of 3 months was 32%. At the 20 mg level, there was 1 complete
response and 13 partial responses. With the 50 mg dose, there were no
complete responses and 14 partial responses.
The clinical benefit rate (complete and partial responses plus stable
disease for at least 6 months) was 50% in the patients receiving 20
mg and 52% in those receiving 50 mg. The clinical benefit rate was
58% in patients with locally advanced disease and 47% in patients
with metastatic disease.
Toxicities were generally minimal, with no differences between the
dose levels. Overall, the most common side effect was hot flashes.
It is important to mention that of these almost 90 patients,
only one case of endometrial hyperplasia was observed, and it was
benign, he said.
Dr. Baselga concluded that LY353381 demonstrated tumor activity
and clinical benefit at both the 20 mg and 50 mg dose level, with no
significant differences in either efficacy or toxicity observed
between the two dose levels. In light of this, Dr. Baselga
said, multinational, randomized, phase III trials of LY353381 vs
tamoxifen are planned in the metastatic and adjuvant settings.