Ruhstaller T, et al. - The long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years were analyzed. BIG 1-98 is a four-arm, phase III, double-blind, randomized trial that compared 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. Letrozole was continuously favoured by trends in efficacy end points. In the first 10 years, reduction in contralateral breast cancer frequency was observed in correlation with letrozole, however, this reversed beyond 10 years. This study establishes the value of extended follow-up in trials of luminal breast cancer.

Methods

• At 8.4 years of median follow-up, the pharmaceutical company sponsorship ended; at this point academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events.
• The Danish Breast Cancer Cooperative Group Registry was analyzed for the information from Denmark.
• Reporting was made of intention-to-treat analyses.

Results

• Eight thousand ten patients were enrolled; of these, 4,433 were alive and not withdrawn at an LTFU participating center; at least one LTFU report was available of 3,833 (86%) patients.
• While comparing monotherapy with 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.
• Significant variation in efficacy of letrozole vs tamoxifen for contralateral breast cancer over time was observed(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, seemingly more effective reporting of specific long-term adverse events is possible than with case-record reporting of clinical follow-up.