SAN ANTONIO — Switching postmenopausal breast cancer patients to an aromatase inhibitor following 2–3 years of adjuvant tamoxifen results in markedly better disease-free survival than the traditional 5 full years of tamoxifen, according to three major randomized trials presented at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
Raimund Jakesz, M.D., recommended that breast cancer patients who fit the profile of participants in two European clinical trials he reported on at the conference be routinely switched to 3 years of anastrozole (Arimidex) after 2 years of tamoxifen.
He reported on more than 3,100 breast cancer patients in the AstraZeneca-sponsored Austrian Breast and Colorectal Cancer Study Group Trial 8 and the German Adjuvant Breast Cancer Group ARNO 95 study who were randomized to the standard 5 years of adjuvant tamoxifen or to 2 years of tamoxifen followed by 3 years of anastrozole.
The 3-year rate of freedom from locoregional recurrence, distant metastasis, and contralateral breast cancer was 95.8% with tamoxifen/anastrozole vs. 92.7% with tamoxifen. The likelihood of survival free of distant recurrence was 39% greater with tamoxifen followed by anastrozole, said Dr. Jakesz, professor of surgery at the University of Vienna.
All participants in the two randomized trials were postmenopausal, had hormone receptor-positive disease, and underwent breast-conserving therapy. One-fourth were node positive. None received chemotherapy. Forty percent were under 60 years old. Most had small, well-differentiated tumors.
In a separate presentation, Charles Coombes, M.D., gave an update on the Intergroup Exemestane Study (IES), in which 4,740 postmenopausal breast cancer patients were randomized to 5 years of adjuvant tamoxifen or switched to exemestane (Aromasin) after 2–3 years. At a median 37 months' follow-up, local or distant recurrence had developed in 264 women treated with tamoxifen and 193 switched to the aromatase inhibitor. That translated into a 27% increase in disease-free survival in patients who switched. Twelve cases of contralateral breast cancer occurred in the tamoxifen/exemestane group vs. 26 in those on tamoxifen alone.
A particularly intriguing finding is that there have been significantly fewer new primary cancers at sites other than the breast with exemestane: 46 vs. 59 in the tamoxifen-only arm. There have been 6 cases of lung cancer with tamoxifen/exemestane vs. 13 with tamoxifen, and 2 cases of melanoma vs. 5 cases with tamoxifen only. However, 20 acute MIs have occurred in patients switched to the aromatase inhibitor vs. 8 MIs in the tamoxifen-only group, said Dr. Coombes, director of the Cancer Research UK Laboratories at Imperial College, London.
Based upon the highly favorable IES data, Pfizer announced it has submitted a supplemental New Drug Application seeking Food and Drug Administration approval for exemestane as adjuvant therapy in postmenopausal women with hormone receptor-positive early-stage breast cancer. At present, tamoxifen and anastrozole are the sole drugs with that indication.
A midcourse switch from tamoxifen to an aromatase inhibitor makes a lot of sense, Hope S. Rugo, M.D., said at a satellite symposium held in conjunction with the San Antonio conference. Tamoxifen is of proven benefit in preventing recurrent breast cancer. It's a good drug with favorable ancillary effects on bone mineral density and the cardiovascular risk profile. But resistance can occur as early as 12–18 months after starting.
Plus, the most serious side effects associated with tamoxifen—endometrial cancer and thromboembolism—become more likely with longer treatment. Stopping tamoxifen early might prevent some of these major adverse events while still providing protection against the increased fracture risk associated with 5 years of anastrozole in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, said Dr. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco, Comprehensive Cancer Center.
To date the switch trials have shown a higher incidence of osteoporosis but not a significant rise in fractures, compared with 5 years of tamoxifen alone, she noted.