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, István; Colleoni, Marco; Thürlimann, Beat (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, 34(21), pp. 2452-2459. American Society of Clinical Oncology 10.1200/JCO.2015.63.8619

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Rabaglio, Manuela Elena

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0732-183X

Publisher:

American Society of Clinical Oncology

Language:

English

Submitter:

Marianne Zahn

Date Deposited:

06 Jan 2017 16:49

Last Modified:

02 Mar 2023 23:28

Publisher DOI:

10.1200/JCO.2015.63.8619

PubMed ID:

27217455

BORIS DOI:

10.7892/boris.92581

URI:

https://boris.unibe.ch/id/eprint/92581

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