Toremifene Appears Equivalent to Tamoxifen as Adjuvant Therapy for Breast Cancer: Interim Analysis

TAMPERE, Finland—Adjuvant treatment with the nonsteroidal estrogen inhibitor toremifene (Fareston) proved equivalent to tamoxifen (Nolvadex) for prevention of breast cancer recurrence but was associated with fewer embolic events, investigators in an ongoing Finnish trial reported at the San Antonio Breast Cancer Symposium.

Over a mean follow-up of 2.7 years, patients treated with toremifene had an 18.3% recurrence rate, compared with 21.6% for tamoxifen (P = .26). Toremifene patients had a lower overall incidence of embolic events and a significantly lower incidence of cerebrovascular events.

“At this point, we really don’t have a good explanation for the difference in embolic events,” said Kaija Holli, MD, an oncologist at Tampere University Hospital. “We have started an additional trial to learn more about the effects of toremifene on the clotting system.”

Dr. Holli reported findings on the first 900 patients enrolled in a study that ultimately will accrue a total of 1,460 patients.

All the patients are postmenopausal and have histologically verified invasive breast cancer with spread to the axillary lymph nodes. More than 60% of the women are estrogen-receptor positive. Patients undergo segmental mastectomy and axillary lymph node dissection. Patients are randomized to receive 40 mg of toremifene daily or 20 mg of tamoxifen daily. Treatment continues for 3 years.

At the interim follow-up, the two agents proved equivalent in their ability to prevent breast cancer recurrence. Dr. Holli said that 84 of 459 evaluable toremifene patients have had recurrences (11 locoregional, 73 distant) vs 95 of 440 tamoxifen patients (7 locoregional, 88 distant).

Analysis of cardiovascular events showed a trend in favor of toremifene-treated patients. Overall, 19 toremifene patients have had events, resulting in an incidence of 4.1%, compared with a 6.4% incidence in the tamoxifen group. The major difference related to cerebrovascular events, which occurred in 0.4% of toremifene patients and 2.5% of tamoxifen patients (P = .01).

“There were fewer cardiovascular events in the toremifene patients,” Dr. Holli said. “We carefully recorded all possible adverse events. There is something going on with respect to these events, but we cannot say what the reason is. We found the difference between toremifene and tamoxifen very interesting.”

The Finnish investigators have planned other comparative trials involving toremifene and tamoxifen. The trials will incorporate careful scrutiny of lipid levels, endometrial changes, bone density, and ocular changes. Dr. Holli said results could be available within a year.

Dual Action

“Tamoxifen has been shown to reduce recurrences and subsequent mortality from breast cancer but also has emerged with a variety of unexpected effects, some of which are adverse,” she commented.

Part of the effects have been explained by the dual antiestrogenic and estrogenic action of tamoxifen, she said. “Toremifene has similar antiestrogenic and estrogenic effects, but it has a lower estrogenic-to-antiestrogenic ratio than tamoxifen, which might help explain differences between the two drugs, including the differences we observed in this study.”