ASCO Even after 8 years, elderly postmenopausal
women who had osteoporosis treated with the selective estrogen-receptor
modulator raloxifene (Evista) continued to realize a significant benefit in
terms of reduced risk of invasive breast cancer, according to Silvana Martino,
DO, who presented data on more than 7,000 women from two related clinical
Emphasizing that Evista is only indicated for prevention and
treatment of postmenopausal osteoporosis, Dr. Mar-tino, a medical oncologist at
John Wayne Cancer Institute, Santa Monica, California, presented the findings
at the 40th Annual Meeting of the American Society of Clinical Oncology
She discussed data from the 4-year CORE (Continuing Outcomes
Relevant to Evista) trial, a follow-up with continued observation of women who
had already participated for 4 years in the MORE (Multiple Outcomes of
Raloxifene) trial, as well as combined results across the 8-year study period.
MORE was a randomized, double-blind, placebo-controlled
osteoporosis treatment trial in postmenopausal women without a history of
breast cancer, to determine as a secondary endpoint whether postmenopausal
women on raloxifene had a lower risk of invasive breast cancer. The 3-year
treatment phase was followed by a 1-year extension.
A total of 7,705 women (mean age 66.5 years, 96% Caucasian)
taking raloxifene or placebo were followed for a median of 48 months, from 1994
through 1998, at 180 clinical centers in 25 countries, mainly in the United
States and Europe. Participants received 120 mg of raloxifene daily (two 60-mg
tablets); or 60 mg of raloxifene daily (one 60-mg tablet plus one placebo
tablet); or two placebo tablets.
During the MORE study period, treatment with raloxifene
reduced the risk of invasive breast cancer by 72% among postmenopausal women
with osteoporosis. The MORE investigators determined that, to prevent 1 case of
invasive breast cancer, 93 osteoporotic women would need to be treated with
The CORE trial began on Jan. 1, 1999, as an additional
4-year follow-up to the MORE trial, but with invasive breast cancer reduction
as the primary endpoint, Dr. Martino said. The 4,011 participants in MORE who
were screened and consented to participate in CORE were not re-randomized; they
retained the randomization to which they had originally been assigned in the
MORE trial, with two thirds assigned to raloxifene and one third assigned to
placebo. However, all CORE patients assigned to raloxifene received the same
dose, 60 mg/d. There was a brief period (median 10.6 months) between MORE and
CORE during which no patients received treatment.
"An additional 1,217 women at these same sites were
completing their MORE trial participation when CORE was being designed," Dr.
Martino said. "By study design, their breast cancer data are encompassed in
CORE as part of the CORE time period starting in January 1999."
Data on 5,213 women were available for analysis. A total of
52 cases of invasive breast cancer were identified: 28 in the placebo group (n
= 1,703) and 24 in the raloxifene group (n = 3,510). The incidence of invasive
breast cancer in the raloxifene group was 59% lower than in the placebo group
(hazard ratio 0.41, 95% CI 0.24-0.71; P < .001). Estrogen-receptor
status was determined for 46 of the women with invasive breast cancer; the
incidence of ER-positive invasive breast cancer was reduced by 66% with
raloxifene. Use of raloxifene did not affect the incidence of ER-negative
The combined data show that 8 years of raloxifene in the
MORE and CORE trials was associated with a 66% reduction in the risk of
invasive breast cancer overall and a 76% reduction in the risk of invasive
ER-positive breast cancer. The combined data show that 69 women would need to
be treated with raloxifene to prevent 1 case of invasive breast cancer during
that time span, she said.
"Whether one looks at the MORE trial, or the CORE trial, or
the two combined, the same biology is observedthat, yes, this agent does have
the ability to reduce the incidence and the risk of breast cancer," she said at
a press conference held during the ASCO meeting. "The reduction in breast
cancer incidence appears to be specific to ER-positive breast cancer, with no
difference noted in ER-negative breast cancer; nor did we see any difference in
noninvasive breast cancer."
Safety data were derived from assessment of the 4,011 women
who participated in MORE and CORE for the entire 8 years of those studies.
Importantly, she said, over the 8 years of treatment, there was no increased
risk of vaginal bleeding, endometrial hyperplasia, or endometrial cancer with
raloxifene use. Although hot flushes and leg cramps were more common with
raloxifene than placebo, these occurred with greater frequency during the MORE
trial (years 1-4) in the raloxi-fene group but were equal during years 5-8
between the two groups. Dr. Martino noted that there were no new toxicities
identified in the CORE trial.
A twofold increase in risk of venous thromboembolism with raloxifene vs
placebo persisted over the 8-year study period, but this increased risk was
small and did not reach significance, Dr. Martino said. This is an important
issue to consider, particularly in sedentary patients, she noted, but added
that "these still are rare events." The increased incidence of pulmonary emboli
with raloxifene was significant: 0.2% in the placebo group vs 0.6% in the
raloxifene group (P = .048). However, she noted that "overall, the drug
is easy to use and quite safe," with no increased incidence of arterial
thrombotic events such as stroke or myocardial infarction.