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Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial.
Breast Cancer Res Treat. 2006 Oct; 99(3):295-300.BC

Abstract

PURPOSE

MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes.

METHODS

The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate.

RESULTS

Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p < 0.0001 and p = 0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p = 0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p = 0.027) whereas the HRs for DDFS and OS showed no significant change over time.

CONCLUSION

These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting.

Authors+Show Affiliations

Ingle JN
Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
Tu D
No affiliation info available
Pater JL
No affiliation info available
Martino S
No affiliation info available
Robert NJ
No affiliation info available
Muss HB
No affiliation info available
Piccart MJ
No affiliation info available
Castiglione M
No affiliation info available
Shepherd LE
No affiliation info available
Pritchard KI
No affiliation info available
Livingston RB
No affiliation info available
Davidson NE
No affiliation info available
Norton L
No affiliation info available
Perez EA
No affiliation info available
Abrams JS
No affiliation info available
Cameron DA
No affiliation info available
Palmer MJ
No affiliation info available
Goss PE
No affiliation info available

MeSH

AgedAntineoplastic AgentsAromatase InhibitorsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDouble-Blind MethodDrug Administration ScheduleFemaleHumansLetrozoleMiddle AgedNitrilesPostmenopauseProportional Hazards ModelsReceptors, EstrogenReceptors, ProgesteroneSelective Estrogen Receptor ModulatorsSurvival AnalysisTamoxifenTime FactorsTreatment OutcomeTriazoles

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16541302

Clinical Trial Links

Letrozole After Tamoxifen in Treating Women With Breast Cancer

Citation

Ingle, James N., et al. "Duration of Letrozole Treatment and Outcomes in the Placebo-controlled NCIC CTG MA.17 Extended Adjuvant Therapy Trial." Breast Cancer Research and Treatment, vol. 99, no. 3, 2006, pp. 295-300.
Ingle JN, Tu D, Pater JL, et al. Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. Breast Cancer Res Treat. 2006;99(3):295-300.
Ingle, J. N., Tu, D., Pater, J. L., Martino, S., Robert, N. J., Muss, H. B., Piccart, M. J., Castiglione, M., Shepherd, L. E., Pritchard, K. I., Livingston, R. B., Davidson, N. E., Norton, L., Perez, E. A., Abrams, J. S., Cameron, D. A., Palmer, M. J., & Goss, P. E. (2006). Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. Breast Cancer Research and Treatment, 99(3), 295-300.
Ingle JN, et al. Duration of Letrozole Treatment and Outcomes in the Placebo-controlled NCIC CTG MA.17 Extended Adjuvant Therapy Trial. Breast Cancer Res Treat. 2006;99(3):295-300. PubMed PMID: 16541302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. AU - Ingle,James N, AU - Tu,Dongsheng, AU - Pater,Joseph L, AU - Martino,Silvana, AU - Robert,Nicholas J, AU - Muss,Hyman B, AU - Piccart,Martine J, AU - Castiglione,Monica, AU - Shepherd,Lois E, AU - Pritchard,Kathleen I, AU - Livingston,Robert B, AU - Davidson,Nancy E, AU - Norton,Larry, AU - Perez,Edith A, AU - Abrams,Jeffrey S, AU - Cameron,David A, AU - Palmer,Michael J, AU - Goss,Paul E, Y1 - 2006/03/16/ PY - 2006/02/14/received PY - 2006/02/16/accepted PY - 2006/3/17/pubmed PY - 2007/1/20/medline PY - 2006/3/17/entrez SP - 295 EP - 300 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 99 IS - 3 N2 - PURPOSE: MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes. METHODS: The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate. RESULTS: Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p < 0.0001 and p = 0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p = 0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p = 0.027) whereas the HRs for DDFS and OS showed no significant change over time. CONCLUSION: These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting. SN - 0167-6806 UR - https://www.unboundmedicine.com/medline/citation/16541302/Duration_of_letrozole_treatment_and_outcomes_in_the_placebo_controlled_NCIC_CTG_MA_17_extended_adjuvant_therapy_trial_ DB - PRIME DP - Unbound Medicine ER -