Letrozole More Effective than Tamoxifen in Postmenopausal Breast Cancer
The Breast International Group (BIG) 1-98 is a randomized, phase 3, double-blind clinical trial that includes 8010 postmenopausal women with early-stage hormone receptor–positive breast cancer. The current study reports the median 8.1-year follow-up outcomes of the BIG 1-98, reflecting the long-term risk for recurrence and death in this patient population (Regan MM, et al. Lancet Oncol. 2011; 12:1101-1108).
A total of 2459 patients were randomized to monotherapy with letrozole or tamoxifen for 5 years. In the 4- arm option, 6182 patients were randomized to 1 of 4 sequential therapy groups, beginning either one drug (tamoxifen or letrozole) for 3 years followed by the other drug (tamoxifen or letrozole) for 2 years; or 2 years with the first drug followed by 3 years with the other drug. In 2005, after a significant disease-free survival (DFS) benefit was reported with letrozole, the study protocol was amended to allow patients to cross over from tamoxifen therapy to letrozole therapy. The final treatment phase ended in 2008.
The primary study end point was DFS. Secondary end points were OS, distant recurrence-free interval, and invasive breast cancer–free interval.
After a median follow-up period of 8.1 years, 2074 patients showed DFS compared with 1569 patients showing DFS by the protocol-specified update in 2009. The additional 505 events (a 32% increase) occurred between 2003 and 2011, in the latter phases of the study. In addition, 5936 (74%) of the patients were reported to be alive and without a DFS event at their most recent follow-up. At a median followup of 8.7 years, letrozole monotherapy continued to show significantly better DFS compared with tamoxifen monotherapy. Sequential treatment with one drug then the other did not improve DFS compared with letrozole monotherapy in patients with breast cancer–free interval or distant recurrence– free interval.
With more than 8 years of followup, this study confirms that letrozole is more effective than tamoxifen in the long-term management of early-stage postmenopausal breast cancer