Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial

James N. Ingle, Dongsheng Tu, Joseph L. Pater, Silvana Martino, Nicholas J. Robert, Hyman B. Muss, Martine J. Piccart, Monica Castiglione, Lois E. Shepherd, Kathleen I. Pritchard, Robert B Livingston, Nancy E. Davidson, Larry Norton, Edith A. Perez, Jeffrey S. Abrams, David A. Cameron, Michael J. Palmer, Paul E. Goss

Research output: Contribution to journalArticle

78 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)295-300
Number of pages6
JournalBreast Cancer Research and Treatment
Volume99
Issue number3
DOIs
StatePublished - Oct 2006
Externally publishedYes

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letrozole
Placebos
Disease-Free Survival
Survival
Therapeutics
Tamoxifen
Proportional Hazards Models
Databases

Keywords

  • Adjuvant hormonal therapy
  • Early breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. / Ingle, James N.; Tu, Dongsheng; Pater, Joseph L.; Martino, Silvana; Robert, Nicholas J.; Muss, Hyman B.; Piccart, Martine J.; Castiglione, Monica; Shepherd, Lois E.; Pritchard, Kathleen I.; Livingston, Robert B; Davidson, Nancy E.; Norton, Larry; Perez, Edith A.; Abrams, Jeffrey S.; Cameron, David A.; Palmer, Michael J.; Goss, Paul E.

In: Breast Cancer Research and Treatment, Vol. 99, No. 3, 10.2006, p. 295-300.

Research output: Contribution to journalArticle

Ingle, JN, Tu, D, Pater, JL, Martino, S, Robert, NJ, Muss, HB, Piccart, MJ, Castiglione, M, Shepherd, LE, Pritchard, KI, Livingston, RB, Davidson, NE, Norton, L, Perez, EA, Abrams, JS, Cameron, DA, Palmer, MJ & Goss, PE 2006, '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, pp. 295-300. https://doi.org/10.1007/s10549-006-9207-y
Ingle, James N. ; Tu, Dongsheng ; Pater, Joseph L. ; Martino, Silvana ; Robert, Nicholas J. ; Muss, Hyman B. ; Piccart, Martine J. ; Castiglione, Monica ; Shepherd, Lois E. ; Pritchard, Kathleen I. ; Livingston, Robert B ; Davidson, Nancy E. ; Norton, Larry ; Perez, Edith A. ; Abrams, Jeffrey S. ; Cameron, David A. ; Palmer, Michael J. ; Goss, Paul E. / Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. In: Breast Cancer Research and Treatment. 2006 ; Vol. 99, No. 3. pp. 295-300.
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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.",
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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.

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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.

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KW - Early breast cancer

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