Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor
2-positive breast cancer: planned joint analysis of overall survival from NSABP
B-31 and NCCTG N9831.
Author(s): Perez EA(1), Romond EH(2), Suman VJ(2), Jeong JH(2), Sledge G(2), Geyer CE Jr(2),
Martino S(2), Rastogi P(2), Gralow J(2), Swain SM(2), Winer EP(2), Colon-Otero
G(2), Davidson NE(2), Mamounas E(2), Zujewski JA(2), Wolmark N(2).
Affiliation(s): Author information:
(1)Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville;
Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health,
Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J.
Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of
Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman
Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford
University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and
Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth
University Massey Cancer Center, Richmond, VA; Julie Gralow, University of
Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar
Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer
Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health,
Rockville, MD. perez.edith@mayo.edu. (2)Edith A. Perez, Gerardo Colon-Otero, the
Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health
Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of
Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon
Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of
Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital,
Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford;
Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA;
Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center,
Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care
Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center,
Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne
Zujewski, National Institutes of Health, Rockville, MD.
Publication date & source: 2014, J Clin Oncol. , 32(33):3744-52
PURPOSE: Positive interim analysis findings from four large adjuvant trials
evaluating trastuzumab in patients with early-stage human epidermal growth factor
receptor 2 (HER2) -positive breast cancer were first reported in 2005. One of
these reports, the joint analysis of North Central Cancer Treatment Group NCCTG
N9831 (Combination Chemotherapy With or Without Trastuzumab in Treating Women
With HER2-Overexpressing Breast Cancer) and the National Surgical Adjuvant Breast
and Bowel Project NSABP B-31 (Doxorubicin and Cyclophosphamide Plus Paclitaxel
With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer
That Overexpresses HER2), was updated in 2011. We now report the planned
definitive overall survival (OS) results from this joint analysis along with
updates on the disease-free survival (DFS) end point.
METHODS: In all, 4,046 patients with HER2-positive operable breast cancer were
enrolled to receive doxorubicin and cyclophosphamide followed by paclitaxel with
or without trastuzumab in both trials. The required number of events for the
definitive statistical analysis for OS (710 events) was reached in September
2012. Updated analyses of overall DFS and related subgroups were also performed.
RESULTS: Median time on study was 8.4 years. Adding trastuzumab to chemotherapy
led to a 37% relative improvement in OS (hazard ratio [HR], 0.63; 95% CI, 0.54 to
0.73; P < .001) and an increase in 10-year OS rate from 75.2% to 84%. These
results were accompanied by an improvement in DFS of 40% (HR, 0.60; 95% CI, 0.53
to 0.68; P < .001) and increase in 10-year DFS rate from 62.2% to 73.7%. All
patient subgroups benefited from addition of this targeted anti-HER2 agent.
CONCLUSION: The addition of trastuzumab to paclitaxel after doxorubicin and
cyclophosphamide in early-stage HER2-positive breast cancer results in a
substantial and durable improvement in survival as a result of a sustained marked
reduction in cancer recurrence.
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