Disease-Free and Overall Survival among Patients with Operable HER2-Positive Breast Cancer Treated with Sequential vs Concurrent Chemotherapy

The ACOSOG Z1041 (Alliance) Randomized Clinical Trial

Aman U. Buzdar, Vera J. Suman, Funda Meric-Bernstam, Ann Marilyn Leitch, Matthew J. Ellis, Judy C. Boughey, Gary W. Unzeitig, Melanie E. Royce, Kelly K. Hunt

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Importance: Pathologic complete response rate (pCR), the primary end point of the ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens. Objective: To assess DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab. Design, Setting, and Participants: Phase 3 randomized clinical trial conducted at 36 centers in the continental United States and Puerto Rico. Women 18 years or older with invasive operable HER2-positive breast cancer were enrolled from September 15, 2007, to December 15, 2011, and randomized to 1 of 2 treatment arms. The analysis data set was locked on October 15, 2017, and analysis was completed on December 15, 2017. Interventions: Patients randomized to arm 1 received 500 mg/m2 of fluorouracil, 75 mg/m2 of epirubicin, and 500 mg/m2 of cyclophosphamide (FEC) every 3 weeks for 12 weeks followed by the combination of 80 mg/m2 of paclitaxel and 2 mg/kg (except initial dose of 4 mg/kg) of trastuzumab weekly for 12 weeks. Patients randomized to arm 2 received the same combination of paclitaxel with trastuzumab weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12 weeks. Women with hormone receptor-positive disease received endocrine therapy, and radiotherapy was delivered at physician discretion. Main Outcomes and Measures: The primary outcomes were DFS and OS and pCR in the breast and nodes. Results: Two hundred eighty-two women with HER2-positive breast cancer were enrolled in the trial, and 2 withdrew consent before treatment. Among the remaining 280 women, the median age was 50 years (range, 28-76 years), 232 (82.9%) were white, 29 (10.3%) were black, 8 (2.9%) were Asian, 4 (1.4%) were American Indian or Alaskan Native, and 7 (2.5%) did not report race/ethnicity. There were 22 disease events in arm 1 and 27 in arm 2. Disease-free survival rates did not differ with respect to treatment arm (stratified log-rank P =.96; stratified hazard ratio [HR] [arm 2 to arm 1], 1.02; 95% CI, 0.56-1.83). Overall survival did not differ with respect to treatment arm (stratified log-rank P =.73; stratified HR [arm 2 to arm 1], 1.17; 95% CI, 0.48-2.88). Conclusions and Relevance: Across a median follow-up of 5.1 years (range, 26 days to 6.2 years), pCR, DFS, and OS did not differ with respect to sequential or concurrent administration of FEC with trastuzumab. Trial Registration: ClinicalTrials.gov identifier: NCT00513292.

Original languageEnglish (US)
Pages (from-to)E1-E6
JournalJAMA oncology
DOIs
StateAccepted/In press - Jan 1 2018

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Disease-Free Survival
Arm
Randomized Controlled Trials
Breast Neoplasms
Drug Therapy
Survival
Paclitaxel
Surgeons
Therapeutics
Endocrine System Diseases
Puerto Rico
Epirubicin
Phase III Clinical Trials
North American Indians
Anthracyclines
Fluorouracil
Cyclophosphamide
Breast
Radiotherapy
Survival Rate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Disease-Free and Overall Survival among Patients with Operable HER2-Positive Breast Cancer Treated with Sequential vs Concurrent Chemotherapy : The ACOSOG Z1041 (Alliance) Randomized Clinical Trial. / Buzdar, Aman U.; Suman, Vera J.; Meric-Bernstam, Funda; Leitch, Ann Marilyn; Ellis, Matthew J.; Boughey, Judy C.; Unzeitig, Gary W.; Royce, Melanie E.; Hunt, Kelly K.

In: JAMA oncology, 01.01.2018, p. E1-E6.

Research output: Contribution to journalArticle

Buzdar, Aman U. ; Suman, Vera J. ; Meric-Bernstam, Funda ; Leitch, Ann Marilyn ; Ellis, Matthew J. ; Boughey, Judy C. ; Unzeitig, Gary W. ; Royce, Melanie E. ; Hunt, Kelly K. / Disease-Free and Overall Survival among Patients with Operable HER2-Positive Breast Cancer Treated with Sequential vs Concurrent Chemotherapy : The ACOSOG Z1041 (Alliance) Randomized Clinical Trial. In: JAMA oncology. 2018 ; pp. E1-E6.
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abstract = "Importance: Pathologic complete response rate (pCR), the primary end point of the ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens. Objective: To assess DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab. Design, Setting, and Participants: Phase 3 randomized clinical trial conducted at 36 centers in the continental United States and Puerto Rico. Women 18 years or older with invasive operable HER2-positive breast cancer were enrolled from September 15, 2007, to December 15, 2011, and randomized to 1 of 2 treatment arms. The analysis data set was locked on October 15, 2017, and analysis was completed on December 15, 2017. Interventions: Patients randomized to arm 1 received 500 mg/m2 of fluorouracil, 75 mg/m2 of epirubicin, and 500 mg/m2 of cyclophosphamide (FEC) every 3 weeks for 12 weeks followed by the combination of 80 mg/m2 of paclitaxel and 2 mg/kg (except initial dose of 4 mg/kg) of trastuzumab weekly for 12 weeks. Patients randomized to arm 2 received the same combination of paclitaxel with trastuzumab weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12 weeks. Women with hormone receptor-positive disease received endocrine therapy, and radiotherapy was delivered at physician discretion. Main Outcomes and Measures: The primary outcomes were DFS and OS and pCR in the breast and nodes. Results: Two hundred eighty-two women with HER2-positive breast cancer were enrolled in the trial, and 2 withdrew consent before treatment. Among the remaining 280 women, the median age was 50 years (range, 28-76 years), 232 (82.9{\%}) were white, 29 (10.3{\%}) were black, 8 (2.9{\%}) were Asian, 4 (1.4{\%}) were American Indian or Alaskan Native, and 7 (2.5{\%}) did not report race/ethnicity. There were 22 disease events in arm 1 and 27 in arm 2. Disease-free survival rates did not differ with respect to treatment arm (stratified log-rank P =.96; stratified hazard ratio [HR] [arm 2 to arm 1], 1.02; 95{\%} CI, 0.56-1.83). Overall survival did not differ with respect to treatment arm (stratified log-rank P =.73; stratified HR [arm 2 to arm 1], 1.17; 95{\%} CI, 0.48-2.88). Conclusions and Relevance: Across a median follow-up of 5.1 years (range, 26 days to 6.2 years), pCR, DFS, and OS did not differ with respect to sequential or concurrent administration of FEC with trastuzumab. Trial Registration: ClinicalTrials.gov identifier: NCT00513292.",
author = "Buzdar, {Aman U.} and Suman, {Vera J.} and Funda Meric-Bernstam and Leitch, {Ann Marilyn} and Ellis, {Matthew J.} and Boughey, {Judy C.} and Unzeitig, {Gary W.} and Royce, {Melanie E.} and Hunt, {Kelly K.}",
year = "2018",
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doi = "10.1001/jamaoncol.2018.3691",
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TY - JOUR

T1 - Disease-Free and Overall Survival among Patients with Operable HER2-Positive Breast Cancer Treated with Sequential vs Concurrent Chemotherapy

T2 - The ACOSOG Z1041 (Alliance) Randomized Clinical Trial

AU - Buzdar, Aman U.

AU - Suman, Vera J.

AU - Meric-Bernstam, Funda

AU - Leitch, Ann Marilyn

AU - Ellis, Matthew J.

AU - Boughey, Judy C.

AU - Unzeitig, Gary W.

AU - Royce, Melanie E.

AU - Hunt, Kelly K.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Importance: Pathologic complete response rate (pCR), the primary end point of the ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens. Objective: To assess DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab. Design, Setting, and Participants: Phase 3 randomized clinical trial conducted at 36 centers in the continental United States and Puerto Rico. Women 18 years or older with invasive operable HER2-positive breast cancer were enrolled from September 15, 2007, to December 15, 2011, and randomized to 1 of 2 treatment arms. The analysis data set was locked on October 15, 2017, and analysis was completed on December 15, 2017. Interventions: Patients randomized to arm 1 received 500 mg/m2 of fluorouracil, 75 mg/m2 of epirubicin, and 500 mg/m2 of cyclophosphamide (FEC) every 3 weeks for 12 weeks followed by the combination of 80 mg/m2 of paclitaxel and 2 mg/kg (except initial dose of 4 mg/kg) of trastuzumab weekly for 12 weeks. Patients randomized to arm 2 received the same combination of paclitaxel with trastuzumab weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12 weeks. Women with hormone receptor-positive disease received endocrine therapy, and radiotherapy was delivered at physician discretion. Main Outcomes and Measures: The primary outcomes were DFS and OS and pCR in the breast and nodes. Results: Two hundred eighty-two women with HER2-positive breast cancer were enrolled in the trial, and 2 withdrew consent before treatment. Among the remaining 280 women, the median age was 50 years (range, 28-76 years), 232 (82.9%) were white, 29 (10.3%) were black, 8 (2.9%) were Asian, 4 (1.4%) were American Indian or Alaskan Native, and 7 (2.5%) did not report race/ethnicity. There were 22 disease events in arm 1 and 27 in arm 2. Disease-free survival rates did not differ with respect to treatment arm (stratified log-rank P =.96; stratified hazard ratio [HR] [arm 2 to arm 1], 1.02; 95% CI, 0.56-1.83). Overall survival did not differ with respect to treatment arm (stratified log-rank P =.73; stratified HR [arm 2 to arm 1], 1.17; 95% CI, 0.48-2.88). Conclusions and Relevance: Across a median follow-up of 5.1 years (range, 26 days to 6.2 years), pCR, DFS, and OS did not differ with respect to sequential or concurrent administration of FEC with trastuzumab. Trial Registration: ClinicalTrials.gov identifier: NCT00513292.

AB - Importance: Pathologic complete response rate (pCR), the primary end point of the ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens. Objective: To assess DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab. Design, Setting, and Participants: Phase 3 randomized clinical trial conducted at 36 centers in the continental United States and Puerto Rico. Women 18 years or older with invasive operable HER2-positive breast cancer were enrolled from September 15, 2007, to December 15, 2011, and randomized to 1 of 2 treatment arms. The analysis data set was locked on October 15, 2017, and analysis was completed on December 15, 2017. Interventions: Patients randomized to arm 1 received 500 mg/m2 of fluorouracil, 75 mg/m2 of epirubicin, and 500 mg/m2 of cyclophosphamide (FEC) every 3 weeks for 12 weeks followed by the combination of 80 mg/m2 of paclitaxel and 2 mg/kg (except initial dose of 4 mg/kg) of trastuzumab weekly for 12 weeks. Patients randomized to arm 2 received the same combination of paclitaxel with trastuzumab weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12 weeks. Women with hormone receptor-positive disease received endocrine therapy, and radiotherapy was delivered at physician discretion. Main Outcomes and Measures: The primary outcomes were DFS and OS and pCR in the breast and nodes. Results: Two hundred eighty-two women with HER2-positive breast cancer were enrolled in the trial, and 2 withdrew consent before treatment. Among the remaining 280 women, the median age was 50 years (range, 28-76 years), 232 (82.9%) were white, 29 (10.3%) were black, 8 (2.9%) were Asian, 4 (1.4%) were American Indian or Alaskan Native, and 7 (2.5%) did not report race/ethnicity. There were 22 disease events in arm 1 and 27 in arm 2. Disease-free survival rates did not differ with respect to treatment arm (stratified log-rank P =.96; stratified hazard ratio [HR] [arm 2 to arm 1], 1.02; 95% CI, 0.56-1.83). Overall survival did not differ with respect to treatment arm (stratified log-rank P =.73; stratified HR [arm 2 to arm 1], 1.17; 95% CI, 0.48-2.88). Conclusions and Relevance: Across a median follow-up of 5.1 years (range, 26 days to 6.2 years), pCR, DFS, and OS did not differ with respect to sequential or concurrent administration of FEC with trastuzumab. Trial Registration: ClinicalTrials.gov identifier: NCT00513292.

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