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

Publication

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 Paper/Review - May 23, 2016

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

Citation

Chirgwin J, Colleoni M, Láng I, Neven P, Forbes J, Rabaglio M, Smith I, Goldhirsch A, Gelber R, Debled M, Ejlertsen B, Price K, Coates A, Giobbie-Hurder A, Thürlimann B. 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. J Clin Oncol 2016; 34:2452-9.

Type

Journal Paper/Review (English)

Journal

J Clin Oncol 2016; 34

Publication Date

May 23, 2016

Issn Electronic

1527-7755

Pages

2452-9

Brief description/objective

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.