Randomized trial of standard adjuvant chemotherapy regimens versus capecitabine in older women with early breast cancer: 10-year update of the CALGB 49907 trial

Hyman B. Muss, Mei Yin C. Polley, Donald A. Berry, Heshan Liu, Constance T. Cirrincione, Maria Theodoulou, Ann M. Mauer, Alice B. Kornblith, Ann H. Partridge, Lynn G. Dressler, Harvey J. Cohen, Patricia A. Kartcheske, Edith A. Perez, Antonio C. Wolff, Julie R. Gralow, Harold J. Burstein, Ahmad A. Mahmood, Linda M. Sutton, Gustav Magrinat, Barbara A. ParkerRonald D. Hart, Debjani Grenier, Arti Hurria, Aminah Jatoi, Larry Norton, Clifford A. Hudis, Eric P. Winer, Lisa Carey

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Abstract

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.

Original languageEnglish (US)
Pages (from-to)2338-2348
Number of pages11
JournalJournal of Clinical Oncology
Volume37
Issue number26
DOIs
StatePublished - Sep 10 2019

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Adjuvant Chemotherapy
Breast Neoplasms
Survival
Recurrence
Survival Rate
Hormones
Drug Therapy
Sample Size
Cyclophosphamide
Capecitabine
Second Primary Neoplasms
Methotrexate
Fluorouracil
Doxorubicin
Leukemia
Clinical Trials
Physicians

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Randomized trial of standard adjuvant chemotherapy regimens versus capecitabine in older women with early breast cancer : 10-year update of the CALGB 49907 trial. / Muss, Hyman B.; Polley, Mei Yin C.; Berry, Donald A.; Liu, Heshan; Cirrincione, Constance T.; Theodoulou, Maria; Mauer, Ann M.; Kornblith, Alice B.; Partridge, Ann H.; Dressler, Lynn G.; Cohen, Harvey J.; Kartcheske, Patricia A.; Perez, Edith A.; Wolff, Antonio C.; Gralow, Julie R.; Burstein, Harold J.; Mahmood, Ahmad A.; Sutton, Linda M.; Magrinat, Gustav; Parker, Barbara A.; Hart, Ronald D.; Grenier, Debjani; Hurria, Arti; Jatoi, Aminah; Norton, Larry; Hudis, Clifford A.; Winer, Eric P.; Carey, Lisa.

In: Journal of Clinical Oncology, Vol. 37, No. 26, 10.09.2019, p. 2338-2348.

Research output: Contribution to journalArticle

Muss, HB, Polley, MYC, Berry, DA, Liu, H, Cirrincione, CT, Theodoulou, M, Mauer, AM, Kornblith, AB, Partridge, AH, Dressler, LG, Cohen, HJ, Kartcheske, PA, Perez, EA, Wolff, AC, Gralow, JR, Burstein, HJ, Mahmood, AA, Sutton, LM, Magrinat, G, Parker, BA, Hart, RD, Grenier, D, Hurria, A, Jatoi, A, Norton, L, Hudis, CA, Winer, EP & Carey, L 2019, 'Randomized trial of standard adjuvant chemotherapy regimens versus capecitabine in older women with early breast cancer: 10-year update of the CALGB 49907 trial', Journal of Clinical Oncology, vol. 37, no. 26, pp. 2338-2348. https://doi.org/10.1200/JCO.19.00647
Muss, Hyman B. ; Polley, Mei Yin C. ; Berry, Donald A. ; Liu, Heshan ; Cirrincione, Constance T. ; Theodoulou, Maria ; Mauer, Ann M. ; Kornblith, Alice B. ; Partridge, Ann H. ; Dressler, Lynn G. ; Cohen, Harvey J. ; Kartcheske, Patricia A. ; Perez, Edith A. ; Wolff, Antonio C. ; Gralow, Julie R. ; Burstein, Harold J. ; Mahmood, Ahmad A. ; Sutton, Linda M. ; Magrinat, Gustav ; Parker, Barbara A. ; Hart, Ronald D. ; Grenier, Debjani ; Hurria, Arti ; Jatoi, Aminah ; Norton, Larry ; Hudis, Clifford A. ; Winer, Eric P. ; Carey, Lisa. / Randomized trial of standard adjuvant chemotherapy regimens versus capecitabine in older women with early breast cancer : 10-year update of the CALGB 49907 trial. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 26. pp. 2338-2348.
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abstract = "PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56{\%} and 50{\%}, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88{\%} and 82{\%}, respectively (HR, 0.62; P = .03); and overall survival rates were 62{\%} and 56{\%}, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9{\%} of patients have died (13.1{\%} from breast cancer, 16.4{\%} from causes other than breast cancer, and 14.1{\%} from unknown causes). Second nonbreast cancers occurred in 14.1{\%} of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.",
author = "Muss, {Hyman B.} and Polley, {Mei Yin C.} and Berry, {Donald A.} and Heshan Liu and Cirrincione, {Constance T.} and Maria Theodoulou and Mauer, {Ann M.} and Kornblith, {Alice B.} and Partridge, {Ann H.} and Dressler, {Lynn G.} and Cohen, {Harvey J.} and Kartcheske, {Patricia A.} and Perez, {Edith A.} and Wolff, {Antonio C.} and Gralow, {Julie R.} and Burstein, {Harold J.} and Mahmood, {Ahmad A.} and Sutton, {Linda M.} and Gustav Magrinat and Parker, {Barbara A.} and Hart, {Ronald D.} and Debjani Grenier and Arti Hurria and Aminah Jatoi and Larry Norton and Hudis, {Clifford A.} and Winer, {Eric P.} and Lisa Carey",
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TY - JOUR

T1 - Randomized trial of standard adjuvant chemotherapy regimens versus capecitabine in older women with early breast cancer

T2 - 10-year update of the CALGB 49907 trial

AU - Muss, Hyman B.

AU - Polley, Mei Yin C.

AU - Berry, Donald A.

AU - Liu, Heshan

AU - Cirrincione, Constance T.

AU - Theodoulou, Maria

AU - Mauer, Ann M.

AU - Kornblith, Alice B.

AU - Partridge, Ann H.

AU - Dressler, Lynn G.

AU - Cohen, Harvey J.

AU - Kartcheske, Patricia A.

AU - Perez, Edith A.

AU - Wolff, Antonio C.

AU - Gralow, Julie R.

AU - Burstein, Harold J.

AU - Mahmood, Ahmad A.

AU - Sutton, Linda M.

AU - Magrinat, Gustav

AU - Parker, Barbara A.

AU - Hart, Ronald D.

AU - Grenier, Debjani

AU - Hurria, Arti

AU - Jatoi, Aminah

AU - Norton, Larry

AU - Hudis, Clifford A.

AU - Winer, Eric P.

AU - Carey, Lisa

PY - 2019/9/10

Y1 - 2019/9/10

N2 - PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.

AB - PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.

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