SAN ANTONIONovel regimens pairing gemcitabine (Gemzar) and vinorelbine
(Navelbine) with trastuzumab (Herceptin) showed significant antitumor
activity and good tolerability in heavily pretreated HER-2-positive patients
with metastatic breast cancer, in studies reported at the 24th Annual San
Antonio Breast Cancer Symposium.
"It is becoming increasingly clear that patients with HER-2-positive
metastatic breast cancer will get trastuzumab as the backbone of their
therapy," said Dr. Joyce O’Shaughnessy, a principal investigator of
one of these studies. "We need to determine the contribution of
additional agents to this important treatment."
Dr. O’Shaughnessy, co-director of Breast Cancer Research,
Baylor-Sammons Cancer Center and US Oncology, Dallas, reported the first
results from a multicenter phase II study of 64 heavily pretreated patients
whose breast cancers overexpressed HER-2 at the 2+ or 3+ level by
immunohistochemistry and who had not yet been treated with trastuzumab or
gemcitabine. For 72% of the patients, this novel combination was at least
third-line treatment (abstract 523).
The study evaluated the efficacy and toxicity of gemcitabine 1,200 mg/m²
given weekly for 2 weeks with the third week off on a 21-day cycle, plus
weekly trastuzumab, until disease progression.
Objective partial responses were observed in 22 (37%) of 59 evaluable
patients. Among the 38 patients with 3+ overexpression of HER-2, 17
responded (45%); among the 21 patients with 2+ overexpression, 5 patients
responded (24%). In addition, 22 of the 59 evaluable patients (37%) had
stable disease for a median of 4 months, and the median duration of response
was 5.8 months, Dr. O’Shaughnessy reported.
The combination therapy appeared to boost the response rate above that
achieved with the individual agents in prior studies in heavily treated
patients with gemcitabine and trastuzumab alone. Trastuzumab in late-line
therapy produces about a 15% response rate, and the response to
gemcitabine, in patients pretreated with anthracyclines and taxanes, is
about 10% to 20%, she said.
"Our overall response rate was 37%, so conservatively we can say
that this response may be additive," she commented. "And when we
look at the patients with 3+ overexpression of HER-2, and see a 45% response
rate in very heavily pretreated patients, this would even suggest possible
synergy. A 45% response rate in a multicenter community-based trial is an
impressive result in this patient population."