CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts
Abstract #13
Background: BIG 1-98 compares letrozole (Let), tamoxifen (Tam) and sequences of Let and Tam as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer. Initial results (published in 2005) demonstrated the superiority of Let over Tam in significantly prolonging disease-free survival (DFS) and reducing the risk of relapse in distant sites. Following these results, investigators were informed of the treatment allocation for patients randomized to Tam alone, and about one third of these patients opted to receive Let. The three Let-containing treatments remained blinded. We now evaluate Let and Tam given in sequence compared with Let alone and update the comparison of Let alone and Tam alone. Methods: 6182 patients were randomized to the 4-arm option (entry Sep99-May03) [Tam x 5 years (Tam), Let x 5 (Let), Tam x 2→Let x 3 (Tam→Let), or Let x 2→Tam x 3 (Let→Tam)]. Another 1828 patients were randomized to the 2-arm option (Tam vs. Let; entry Mar98-Mar00). The primary endpoint was DFS (time from randomization to first occurrence of invasive breast cancer recurrence, invasive contralateral breast cancer, second non-breast malignancy, or death from any cause). The presentation will focus on the clinically-relevant comparisons evaluating Tam→Let vs. Let and Let→Tam vs. Let, assessed from the time of randomization. Acknowledging multiple comparisons, the hazard ratios are presented with 99% confidence intervals (CIs). Results: The median follow-up time is 71 months. Hazard ratios comparing treatments from time of initial randomization in terms of DFS, overall survival, and time to distant recurrence are displayed below. ![][1] With this long term follow-up, adverse events for Let and Tam are consistent with the known safety profile of both agents. A protocol-specified update of the previously-reported comparison of Let x 5 vs. Tam x 5 (i.e., the monotherapy arms, including patients in both the 2-arm and 4-arm options; N=4922) suggests improved survival for patients treated with Let (HR=0.87, 95% CI=0.75-1.02, p=0.08, 76 months median follow-up). In this comparison, about a quarter of the patients in the Tam arm crossed over to Let after 3-5 years of Tam. Conclusion: The sequential treatments did not improve DFS compared with Let alone. Trends support initial use of Let in patients at higher risk of relapse. Patients commenced on Let can be switched to Tam if required. Updated results of the monotherapy comparison suggest superior overall survival with Let compared with Tam.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 13.
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