Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

Publication

Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

Journal Paper/Review - Nov 26, 2018

Ruhstaller Thomas, Simoncini Edda, Gianni Lorenzo, Rochlitz Christoph, Kralidis Elena, Zaman Khalil, Jassem Jacek, Piccart-Gebhart Martine, Di Leo Angelo, Gelber Richard D, Coates Alan S, Goldhirsch Aron, Thürlimann Beat, Regan Meredith M, Veyret Corinne, Del Mastro Lucia, Giobbie-Hurder Anita, Colleoni Marco, Jensen Maj-Britt, Ejlertsen Bent, de Azambuja Evandro, Neven Patrick, Láng István, Jakobsen Erik Hugger, Gladieff Laurence, Bonnefoi Hervé, Harvey Vernon J, Spazzapan Simon, Tondini Carlo, members of the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group

Citation

Ruhstaller T, Simoncini E, Gianni L, Rochlitz C, Kralidis E, Zaman K, Jassem J, Piccart-Gebhart M, Di Leo A, Gelber R, Coates A, Goldhirsch A, Thürlimann B, Regan M, Veyret C, Del Mastro L, Giobbie-Hurder A, Colleoni M, Jensen M, Ejlertsen B, de Azambuja E, Neven P, Láng I, Jakobsen E, Gladieff L, Bonnefoi H, Harvey V, Spazzapan S, Tondini C, members of the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group. Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial. J Clin Oncol 2018:JCO1800440.

Type

Journal Paper/Review (English)

Journal

J Clin Oncol 2018

Publication Date

Nov 26, 2018

Issn Electronic

1527-7755

Pages

JCO1800440

Brief description/objective

PURPOSE
Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed 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.

PATIENTS AND METHODS
BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus 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. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported.

RESULTS
Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly 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. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up.

CONCLUSION
Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.