Ruhstaller T, et al. - Long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study were analyzed. Observations revealed reduced contralateral breast cancer frequency in relation to letrozole treatment in the first 10 years. However, this reversed after 10 years, highlighting the significance of extended follow-up in trials of luminal breast cancer.

Methods

• In BIG 1-98, a four-arm, phase 3, double-blind, randomized trial, adjuvant letrozole vs tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer were assessed.
• An observational LTFU extension was initiated by academic partners when pharmaceutical company sponsorship ended at 8.4 years of median follow-up; it comprised collection of annual data on survival, disease status, and adverse events.
• Danish Breast Cancer Cooperative Group Registry provided information from Denmark.
• Reporting of intention-to-treat analyses was done.

Results

• Enrollment of 8,010 patients was done, and of these, 4,433 were alive and not withdrawn at an LTFU participating center; 3,833 (86%) had at least one LTFU report.
• On comparing the monotherapy of letrozole vs tamoxifen, a 9% relative reduction in the hazard of a disease-free survival event with letrozole was noted (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01).
• For other efficacy end points, HRs were similar to those for disease-free survival.
• For contralateral breast cancer, significant variation in efficacy of letrozole vs tamoxifen was noted over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P=.005), perhaps reflecting a longer carryover effect of tamoxifen.
• With national registry, more effective reporting of specific long-term adverse events seemed made than with case-record reporting of clinical follow-up.