ISTANBUL, Turkey--Adding trastuzumab
(Herceptin) to anastrozole
(Arimidex) as adjuvant therapy for postmenopausal
women with so-called copositive
HER2-positive) metastatic breast cancer
signficantly improved progression-free
survival (PFS), compared with anastrozole
alone, according to a study presented
at the 31st Congress of the European
Society for Medical Oncology
(ESMO) (Late Breaking Abstract 2).
Up to 15% of all metastatic breast cancers
are positive for both the estrogen
receptor (ER) and HER2, said lead investigator
Bella Kaufman, MD, of Chaim
Sheba Medical Center, Ramat Gan, Israel.
Evidence of crosstalk between the
estrogen-receptor and HER2 signaling
pathways suggests that simultaneous targeting
of both pathways in women with
co-positive disease may result in greater
antitumor activity than either agent alone,
"Currently, the majority of these
women are treated with chemotherapy
and trastuzumab," she said, "but we
thought it might be possible to achieve
the same result without the toxicity of
chemotherapy. Also, 20% of the ER-positive
population is treated with hormonal
therapy alone, and, for them, the combination
Dr. Kaufman and her colleagues conducted
an open-label, phase III study,
known as TAnDEM and sponsored by
Roche, which markets Herceptin internationally.
They enrolled 208 patients at
77 centers in 22 countries. Eligible patients
were postmenopausal women with
HER2-positive (IHC 3+ and/or FISH+)
and ER-positive and/or progesterone
(PR)-positive metastatic breast cancer.
Patients received anastrozole 1 mg/d
orally or anastrozole plus trastuzumab
4 mg/kg IV infusion on day 1, then 2
mg/kg once weekly, until progression.
Women who progressed on the single
drug were switched to the combination.
Median progression-free survival, the
primary endpoint, doubled with the combination
regimen, from 2.4 months for
those on anastrozole alone to 4.8 months
for those on anastrozole/trastuzumab
(P = .0016). Median overall survival was
also prolonged in the combination arm:
28.5 months vs 23.9 months (P = .325).
"This difference was not statistically
significant," Dr. Kaufman
said. She noted, however, that
the trend toward longer survival
was achieved despite the
fact that 73 patients (35%)
crossed over from the singledrug
arm when their disease
started to progress.
The overall response rate in 147 patients
evaluable for response was threefold
higher with the combination--
20.3% vs 6.8% for anastrozole
alone (P = .018).
"The results are very positive,"
Dr. Kaufman said at an
ESMO press briefing. "In
breast cancer, there are not
many trials that show double
progression-free survival." She
added that the overall safety in both arms
was acceptable, noting that the quality of
life of the women in the trial was most
likely better than if they had been receiving