Excellent outcomes with adjuvant toremifene or tamoxifen in early stage breast cancer.

Abstract

Abstract Abstract #1130 Purpose: Fareston (toremifene) and tamoxifen, both selective estrogen receptor modulators (SERMs), are therapeutically equivalent in treating metastatic breast cancer. We hypothesized that toremifene may have superior therapeutic efficacy as adjuvant therapy for early breast cancer.
 Patients and Methods: The North American Fareston versus Tamoxifen Adjuvant (NAFTA) trial, a multicenter investigator-initiated randomized controlled trial, assigned 1813 female peri- or post-menopausal patients with hormone receptor positive invasive breast cancer to adjuvant treatment with either tamoxifen or toremifene. The primary outcomes evaluated were disease-free survival (DFS), defined as the time from registration to local and/or systemic recurrence, and overall survival (OS), defined as the time from registration until death from any cause. Both an intention-to-treat and a per-protocol analysis were performed.
 Results: Median follow-up was 59 months. The baseline characteristics of the two treatment groups were generally well balanced, although the tamoxifen group tended to be older (median age: 68 vs. 67 years, p=0.096), with larger tumors (median tumor size: 1.3 cm vs. 1.2 cm, p=0.086), of higher grade (proportion Grade 3: 18.3% vs. 15.7%, p=0.081). Based on intention-to-treat, mean OS was not significantly different between tamoxifen and toremifene ((98.1 mo. vs. 98.6 mo., respectively, p=0.628). Similarly, mean DFS was not significantly different between tamoxifen and toremifene (96.4 mo. vs. 96.7 mo., respectively, p=0.790). Controlling for patient age, tumor size, and tumor grade, a Cox multivariate survival analysis found no difference between patients randomized to toremifene vs. tamoxifen in terms of OS (OR = 0.951; 95% CI: 0.623-1.451, p=0.951) or DFS (OR = 1.037; 95% CI: 0.721-1.491, p=0.846). Of the 1813 patients in the study, 104 (5.7%) had a protocol violation after randomization and did not start a study drug. The proportion of such patients was evenly distributed between the tamoxifen and toremifene groups (5.2% vs. 6.3%, respectively, p=0.394). Excluding these patients, survival times were similar between the tamoxifen and toremifene groups (mean OS: 96.401 vs. 96.776, p=0.766; DFS: 98.170 vs. 98.646, p=0.607). Cox proportional hazards models for OS (p=0.951) and DFS (p=0.843) failed to demonstrate a significant difference between the two treatment arms in the per-protocol analysis.
 Conclusions: Women treated with adjuvant hormonal therapy enjoyed excellent DFS and OS. No significant differences were found between treatment with either tamoxifen or toremifene. Treatment of hormone receptor positive patients with either of these SERMs is appropriate. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1130.