Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27 - A randomized controlled phase III trial

Paul E. Goss, James N. Ingle, Kathleen I. Pritchard, Matthew J. Ellis, George W. Sledge, G. Thomas Budd, Manuela Rabaglio, Rafat H. Ansari, David B. Johnson, Richard Tozer, David P. D'Souza, Haji Chalchal, Silvana Spadafora, Vered Stearns, Edith A. Perez, Pedro E R Liedke, Istvan Lang, Catherine Elliott, Karen A. Gelmon, Judy Anne W ChapmanLois E. Shepherd

Research output: Contribution to journalArticle

Abstract

Purpose: In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. Patients and Methods: We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. Results: In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. Conclusion: This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.

Original languageEnglish (US)
Pages (from-to)1398-1404
Number of pages7
JournalJournal of Clinical Oncology
Volume31
Issue number11
DOIs
StatePublished - Apr 10 2013

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exemestane
Breast Neoplasms
Aromatase Inhibitors
Disease-Free Survival
letrozole
Hormones
Bone and Bones
Survival
Uterine Hemorrhage
Metabolic Bone Diseases
Hypertriglyceridemia
Therapeutics
Hypercholesterolemia
Atrial Fibrillation
Androgens
Osteoporosis
anastrozole

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Goss, P. E., Ingle, J. N., Pritchard, K. I., Ellis, M. J., Sledge, G. W., Budd, G. T., ... Shepherd, L. E. (2013). Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27 - A randomized controlled phase III trial. Journal of Clinical Oncology, 31(11), 1398-1404. https://doi.org/10.1200/JCO.2012.44.7805

Exemestane versus anastrozole in postmenopausal women with early breast cancer : NCIC CTG MA.27 - A randomized controlled phase III trial. / Goss, Paul E.; Ingle, James N.; Pritchard, Kathleen I.; Ellis, Matthew J.; Sledge, George W.; Budd, G. Thomas; Rabaglio, Manuela; Ansari, Rafat H.; Johnson, David B.; Tozer, Richard; D'Souza, David P.; Chalchal, Haji; Spadafora, Silvana; Stearns, Vered; Perez, Edith A.; Liedke, Pedro E R; Lang, Istvan; Elliott, Catherine; Gelmon, Karen A.; Chapman, Judy Anne W; Shepherd, Lois E.

In: Journal of Clinical Oncology, Vol. 31, No. 11, 10.04.2013, p. 1398-1404.

Research output: Contribution to journalArticle

Goss, PE, Ingle, JN, Pritchard, KI, Ellis, MJ, Sledge, GW, Budd, GT, Rabaglio, M, Ansari, RH, Johnson, DB, Tozer, R, D'Souza, DP, Chalchal, H, Spadafora, S, Stearns, V, Perez, EA, Liedke, PER, Lang, I, Elliott, C, Gelmon, KA, Chapman, JAW & Shepherd, LE 2013, 'Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27 - A randomized controlled phase III trial', Journal of Clinical Oncology, vol. 31, no. 11, pp. 1398-1404. https://doi.org/10.1200/JCO.2012.44.7805
Goss, Paul E. ; Ingle, James N. ; Pritchard, Kathleen I. ; Ellis, Matthew J. ; Sledge, George W. ; Budd, G. Thomas ; Rabaglio, Manuela ; Ansari, Rafat H. ; Johnson, David B. ; Tozer, Richard ; D'Souza, David P. ; Chalchal, Haji ; Spadafora, Silvana ; Stearns, Vered ; Perez, Edith A. ; Liedke, Pedro E R ; Lang, Istvan ; Elliott, Catherine ; Gelmon, Karen A. ; Chapman, Judy Anne W ; Shepherd, Lois E. / Exemestane versus anastrozole in postmenopausal women with early breast cancer : NCIC CTG MA.27 - A randomized controlled phase III trial. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 11. pp. 1398-1404.
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abstract = "Purpose: In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. Patients and Methods: We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4{\%} improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. Results: In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91{\%} for exemestane and 91.2{\%} for anastrozole (stratified hazard ratio, 1.02; 95{\%} CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6{\%} of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. Conclusion: This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.",
author = "Goss, {Paul E.} and Ingle, {James N.} and Pritchard, {Kathleen I.} and Ellis, {Matthew J.} and Sledge, {George W.} and Budd, {G. Thomas} and Manuela Rabaglio and Ansari, {Rafat H.} and Johnson, {David B.} and Richard Tozer and D'Souza, {David P.} and Haji Chalchal and Silvana Spadafora and Vered Stearns and Perez, {Edith A.} and Liedke, {Pedro E R} and Istvan Lang and Catherine Elliott and Gelmon, {Karen A.} and Chapman, {Judy Anne W} and Shepherd, {Lois E.}",
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T1 - Exemestane versus anastrozole in postmenopausal women with early breast cancer

T2 - NCIC CTG MA.27 - A randomized controlled phase III trial

AU - Goss, Paul E.

AU - Ingle, James N.

AU - Pritchard, Kathleen I.

AU - Ellis, Matthew J.

AU - Sledge, George W.

AU - Budd, G. Thomas

AU - Rabaglio, Manuela

AU - Ansari, Rafat H.

AU - Johnson, David B.

AU - Tozer, Richard

AU - D'Souza, David P.

AU - Chalchal, Haji

AU - Spadafora, Silvana

AU - Stearns, Vered

AU - Perez, Edith A.

AU - Liedke, Pedro E R

AU - Lang, Istvan

AU - Elliott, Catherine

AU - Gelmon, Karen A.

AU - Chapman, Judy Anne W

AU - Shepherd, Lois E.

PY - 2013/4/10

Y1 - 2013/4/10

N2 - Purpose: In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. Patients and Methods: We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. Results: In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. Conclusion: This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.

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