TY - JOUR
T1 - Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer
T2 - Long-Term Follow-Up of the BIG 1-98 Trial
AU - Ruhstaller, Thomas
AU - Giobbie-Hurder, Anita
AU - Colleoni, Marco
AU - Jensen, Maj-Britt
AU - Ejlertsen, Bent
AU - de Azambuja, Evandro
AU - Neven, Patrick
AU - Láng, István
AU - Jakobsen, Erik Hugger
AU - Gladieff, Laurence
AU - Bonnefoi, Hervé
AU - Harvey, Vernon J
AU - Spazzapan, Simon
AU - Tondini, Carlo
AU - Del Mastro, Lucia
AU - Veyret, Corinne
AU - Simoncini, Edda
AU - Gianni, Lorenzo
AU - Rochlitz, Christoph
AU - Kralidis, Elena
AU - Zaman, Khalil
AU - Jassem, Jacek
AU - Piccart-Gebhart, Martine
AU - Di Leo, Angelo
AU - Gelber, Richard D
AU - Coates, Alan S
AU - Goldhirsch, Aron
AU - Thürlimann, Beat
AU - Regan, Meredith M
AU - members of the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group
PY - 2019
Y1 - 2019
N2 - 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 Intention-to-treat analyses are reported.RESULTS: Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report.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.
AB - 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.
KW - Aged
KW - Antineoplastic Agents, Hormonal/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Breast Neoplasms/drug therapy
KW - Chemotherapy, Adjuvant
KW - Disease-Free Survival
KW - Double-Blind Method
KW - Drug Administration Schedule
KW - Female
KW - Humans
KW - Letrozole/administration & dosage
KW - Middle Aged
KW - Postmenopause
KW - Receptors, Estrogen/metabolism
KW - Receptors, Progesterone/metabolism
KW - Tamoxifen/administration & dosage
UR - http://www.scopus.com/inward/record.url?scp=85059747368&partnerID=8YFLogxK
U2 - 10.1200/JCO.18.00440
DO - 10.1200/JCO.18.00440
M3 - Journal article
C2 - 30475668
SN - 0732-183X
VL - 37
SP - 105
EP - 114
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 2
ER -