SAN ANTONIOUpdated results from the Intergroup Exemestane
Study of 4,740 breast cancer patients show adjuvant therapy with the aromatase
inhibitor exemestane (Aromasin) after 2 to 3 years of tamoxifen can cut risk of
recurrence by 30% for women with early-stage breast cancer receiving hormonal
treatment. Patients who switched from tamoxifen to exemestane also had 54%
greater odds of remaining free of contralateral breast cancer, principal
investigator R. Charles Coombes, MD, PhD, said at the 27th Annual San Antonio
Breast Cancer Symposium (abstract 3).
Risk of death from all causes also was lower with exemestane,
but Dr. Coombes said this trend has not reached statistical significance, with
a P value of .08 at a median of 37.4 months of follow-up.
"Exemestane seems better in all subsets of patients, apart
from ER-negative patients," said Dr. Coombes, director of the Cancer Research
UK Laboratories at the Imperial College of Medicine and Hammersmith and Charing
Cross Hospitals, London. The issue is no longer whether to switch from
tamoxifen, he said, but when and for how long to continue with the aromatase
The trial randomized patients who had been successfully
treated for estrogen-receptor (ER)-positive breast cancer after 2 to 3 years of
adjuvant tamoxifen therapy. One group of 2,372 women stayed on tamoxifen for
the remaining 2 to 3 years of hormonal treatment. The second cohort of 2,352
women converted to exemestane for the duration of therapy.
Fewer Deaths, Recurrences
The new data showed fewer breast cancer deaths with
exemestane (95 vs 124 with tamoxifen). Another emerging trend, he said, was
fewer deaths from cancers at other sites with exemestane (46 vs 69), mainly due
to fewer deaths lung and uterine cancer and melanoma. Local recurrences were
reduced with exemestane (43 vs 56), as were distant recurrences (150 vs 208)
and primary contralateral breast cancers (12 vs 26).
Patients in the tamoxifen arm had significantly more
thromboembolic events (69 vs 41 in the exemestane arm) and gynecologic symptoms
(376 vs 301). As expected, incidences of musculoskeletal conditions such as
arthritis, arthralgia, myalgia, and carpal tunnel syndrome were higher for
women on exemestane.
Although the incidence of cardiac deaths was similar in both
arms, myocardial infarctions were more than twice as common in the exemestane
cohort (20 myocardial infarctions vs 8 in the tamoxifen arm). Dr. Coombes noted
that all patients with myocardial infarction had at least one predisposing
factor. "Tamoxifen may be exerting a preventive effect on myocardial
infarction," he said.
The two hormonal agents received similar grades in a
quality-of-life (QOL) report by Lesley Fallowfield, DPhil, who followed a
subgroup of 582 Intergroup Exemestane Study patients (abstract 4). Dr.
Fallowfield, professor of psycho-oncology, Brighton and Sussex Medical School,
Sussex, UK, described quality of life as generally good in this interim report
with follow-up of 24 months, with few differences in self-reports from these
Incidences of hot flashes, night sweats, severe weight gain,
and loss of libido were similar between the two groups, she said. Severe
vaginal discharge was significantly less often a problem with exemestane.
‘The Greater Issue’
The greater issue, she suggested, was loss of libido, which
was a major problem for 32% to 35% of all patients. Similarly, she noted, about
20% of the total patient population complained of night sweats, and 25%
experienced hot flashes. "Individual symptoms, especially vasomotor and sexual
complaints, remain problematic with all endocrine therapy," she commented. "It
behooves us to work energetically to overcome some of these problems."