Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer

Edith A. Perez, Vera Jean Suman, Nancy E. Davidson, Julie R. Gralow, Peter A. Kaufman, Daniel W Visscher, Beiyun Chen, James N. Ingle, Shaker R. Dakhil, JoAnne Zujewski, Alvaro Moreno Aspitia, Thomas M. Pisansky, Robert Brian Jenkins

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Abstract

Purpose: NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2-positive breast cancer. Patients and Methods: Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results: Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion: DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

Original languageEnglish (US)
Pages (from-to)4491-4497
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number34
DOIs
StatePublished - Dec 1 2011

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Adjuvant Chemotherapy
Breast Neoplasms
Disease-Free Survival
Paclitaxel
Survival Rate
Drug Therapy
Trastuzumab
Standard of Care
Doxorubicin
Cyclophosphamide
Odds Ratio
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. / Perez, Edith A.; Suman, Vera Jean; Davidson, Nancy E.; Gralow, Julie R.; Kaufman, Peter A.; Visscher, Daniel W; Chen, Beiyun; Ingle, James N.; Dakhil, Shaker R.; Zujewski, JoAnne; Moreno Aspitia, Alvaro; Pisansky, Thomas M.; Jenkins, Robert Brian.

In: Journal of Clinical Oncology, Vol. 29, No. 34, 01.12.2011, p. 4491-4497.

Research output: Contribution to journalArticle

Perez, Edith A. ; Suman, Vera Jean ; Davidson, Nancy E. ; Gralow, Julie R. ; Kaufman, Peter A. ; Visscher, Daniel W ; Chen, Beiyun ; Ingle, James N. ; Dakhil, Shaker R. ; Zujewski, JoAnne ; Moreno Aspitia, Alvaro ; Pisansky, Thomas M. ; Jenkins, Robert Brian. / Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 34. pp. 4491-4497.
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abstract = "Purpose: NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2-positive breast cancer. Patients and Methods: Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results: Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8{\%} and 80.1{\%}, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95{\%} CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1{\%} and 84.4{\%}, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9{\%} CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion: DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.",
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T1 - Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer

AU - Perez, Edith A.

AU - Suman, Vera Jean

AU - Davidson, Nancy E.

AU - Gralow, Julie R.

AU - Kaufman, Peter A.

AU - Visscher, Daniel W

AU - Chen, Beiyun

AU - Ingle, James N.

AU - Dakhil, Shaker R.

AU - Zujewski, JoAnne

AU - Moreno Aspitia, Alvaro

AU - Pisansky, Thomas M.

AU - Jenkins, Robert Brian

PY - 2011/12/1

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N2 - Purpose: NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2-positive breast cancer. Patients and Methods: Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results: Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion: DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

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