Treatment adherence and its impact on Disease-Free survival in the breast international group 1-98 trial of tamoxifen and letrozole, alone and in sequence

Jacquie H. Chirgwin, Anita Giobbie-Hurder, Alan S. Coates, Karen N. Price, Bent Ejlertsen, Marc Debled, Richard D. Gelber, Aron Goldhirsch, Ian Smith, Manuela Rabaglio, John F. Forbes, Patrick Neven, I. Láng, Marco Colleoni, Beat Thürlimann

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Abstract

Purpose To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. Methods The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Results Both aspects of low adherence (early cessation of letrozole and a compliance score of , 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Conclusion Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence.

Original languageEnglish
Pages (from-to)2452-2459
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number21
DOIs
Publication statusPublished - Jul 20 2016

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letrozole
Tamoxifen
Disease-Free Survival
Breast
Proportional Hazards Models
Therapeutics
Compliance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Treatment adherence and its impact on Disease-Free survival in the breast international group 1-98 trial of tamoxifen and letrozole, alone and in sequence. / Chirgwin, Jacquie H.; Giobbie-Hurder, Anita; Coates, Alan S.; Price, Karen N.; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D.; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F.; Neven, Patrick; Láng, I.; Colleoni, Marco; Thürlimann, Beat.

In: Journal of Clinical Oncology, Vol. 34, No. 21, 20.07.2016, p. 2452-2459.

Research output: Contribution to journalArticle

Chirgwin, JH, Giobbie-Hurder, A, Coates, AS, Price, KN, Ejlertsen, B, Debled, M, Gelber, RD, Goldhirsch, A, Smith, I, Rabaglio, M, Forbes, JF, Neven, P, Láng, I, Colleoni, M & Thürlimann, B 2016, 'Treatment adherence and its impact on Disease-Free survival in the breast international group 1-98 trial of tamoxifen and letrozole, alone and in sequence', Journal of Clinical Oncology, vol. 34, no. 21, pp. 2452-2459. https://doi.org/10.1200/JCO.2015.63.8619
Chirgwin, Jacquie H. ; Giobbie-Hurder, Anita ; Coates, Alan S. ; Price, Karen N. ; Ejlertsen, Bent ; Debled, Marc ; Gelber, Richard D. ; Goldhirsch, Aron ; Smith, Ian ; Rabaglio, Manuela ; Forbes, John F. ; Neven, Patrick ; Láng, I. ; Colleoni, Marco ; Thürlimann, Beat. / Treatment adherence and its impact on Disease-Free survival in the breast international group 1-98 trial of tamoxifen and letrozole, alone and in sequence. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 21. pp. 2452-2459.
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abstract = "Purpose To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. Methods The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Results Both aspects of low adherence (early cessation of letrozole and a compliance score of , 90{\%}) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95{\%} CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95{\%} CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8{\%}; Let-Tam, 20.3{\%}; Tam 16.9{\%}; Let 17.6{\%}). Adverse events were the reason for most trial treatment early discontinuations (82.7{\%}). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Conclusion Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence.",
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AU - Chirgwin, Jacquie H.

AU - Giobbie-Hurder, Anita

AU - Coates, Alan S.

AU - Price, Karen N.

AU - Ejlertsen, Bent

AU - Debled, Marc

AU - Gelber, Richard D.

AU - Goldhirsch, Aron

AU - Smith, Ian

AU - Rabaglio, Manuela

AU - Forbes, John F.

AU - Neven, Patrick

AU - Láng, I.

AU - Colleoni, Marco

AU - Thürlimann, Beat

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N2 - Purpose To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. Methods The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Results Both aspects of low adherence (early cessation of letrozole and a compliance score of , 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Conclusion Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence.

AB - Purpose To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. Methods The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Results Both aspects of low adherence (early cessation of letrozole and a compliance score of , 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Conclusion Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence.

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