SAN ANTONIONovel regimens pairing gemcitabine(Drug information on gemcitabine) (Gemzar) and vinorelbine (Navelbine) with trastuzumab(Drug information on 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."