Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study

Marco Colleoni, Anita Giobbie-Hurder, Meredith M. Regan, Beat Thürlimann, Henning Mouridsen, Louis Mauriac, John F. Forbes, Robert Paridaens, István Láng, Ian Smith, Jacquie Chirgwin, Tadeusz Pienkowski, Andrew Wardley, Karen N. Price, Richard D. Gelber, Alan S. Coates, Aron Goldhirsch

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Abstract

Purpose: Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy. Patients and Methods: Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling. Results: Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P <.05 for DFS, OS, and TDR). Median follow-up was 74 months. Conclusion: Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor - positive breast cancer.

Original languageEnglish
Pages (from-to)1117-1124
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number9
DOIs
Publication statusPublished - Mar 20 2011

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letrozole
Tamoxifen
Breast
Survival
Disease-Free Survival
Recurrence
Breast Neoplasms
Hormones
Therapeutics
Aromatase Inhibitors
Proportional Hazards Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. / Colleoni, Marco; Giobbie-Hurder, Anita; Regan, Meredith M.; Thürlimann, Beat; Mouridsen, Henning; Mauriac, Louis; Forbes, John F.; Paridaens, Robert; Láng, István; Smith, Ian; Chirgwin, Jacquie; Pienkowski, Tadeusz; Wardley, Andrew; Price, Karen N.; Gelber, Richard D.; Coates, Alan S.; Goldhirsch, Aron.

In: Journal of Clinical Oncology, Vol. 29, No. 9, 20.03.2011, p. 1117-1124.

Research output: Contribution to journalArticle

Colleoni, M, Giobbie-Hurder, A, Regan, MM, Thürlimann, B, Mouridsen, H, Mauriac, L, Forbes, JF, Paridaens, R, Láng, I, Smith, I, Chirgwin, J, Pienkowski, T, Wardley, A, Price, KN, Gelber, RD, Coates, AS & Goldhirsch, A 2011, 'Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study', Journal of Clinical Oncology, vol. 29, no. 9, pp. 1117-1124. https://doi.org/10.1200/JCO.2010.31.6455
Colleoni, Marco ; Giobbie-Hurder, Anita ; Regan, Meredith M. ; Thürlimann, Beat ; Mouridsen, Henning ; Mauriac, Louis ; Forbes, John F. ; Paridaens, Robert ; Láng, István ; Smith, Ian ; Chirgwin, Jacquie ; Pienkowski, Tadeusz ; Wardley, Andrew ; Price, Karen N. ; Gelber, Richard D. ; Coates, Alan S. ; Goldhirsch, Aron. / Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 9. pp. 1117-1124.
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abstract = "Purpose: Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy. Patients and Methods: Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2{\%}) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling. Results: Weighted Cox models, by using IPCW, estimated a statistically significant, 18{\%} reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95{\%} CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8{\%} and 90.4{\%} for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95{\%} CI, 0.74 to 0.94) and 0.80 (95{\%} CI, 0.67 to 0.94), respectively (P <.05 for DFS, OS, and TDR). Median follow-up was 74 months. Conclusion: Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor - positive breast cancer.",
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AU - Colleoni, Marco

AU - Giobbie-Hurder, Anita

AU - Regan, Meredith M.

AU - Thürlimann, Beat

AU - Mouridsen, Henning

AU - Mauriac, Louis

AU - Forbes, John F.

AU - Paridaens, Robert

AU - Láng, István

AU - Smith, Ian

AU - Chirgwin, Jacquie

AU - Pienkowski, Tadeusz

AU - Wardley, Andrew

AU - Price, Karen N.

AU - Gelber, Richard D.

AU - Coates, Alan S.

AU - Goldhirsch, Aron

PY - 2011/3/20

Y1 - 2011/3/20

N2 - Purpose: Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy. Patients and Methods: Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling. Results: Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P <.05 for DFS, OS, and TDR). Median follow-up was 74 months. Conclusion: Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor - positive breast cancer.

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