ISTANBUL, Turkey—Adding trastuzumab(Drug information on trastuzumab) (Herceptin) to anastrozole(Drug information on anastrozole) (Arimidex) as adjuvant therapy for postmenopausal women with so-called copositive (hormone-receptor-positive, 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, she explained.
“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 offers benefit.”
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(Drug information on 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 chemotherapy instead.