TY - JOUR
T1 - NSABP B-47/NRG oncology phase III randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER2 by FISH and with IHC 1+ or 2+
AU - Fehrenbacher, Louis
AU - Cecchini, Reena S.
AU - Geyer, Charles E.
AU - Rastogi, Priya
AU - Costantino, Joseph P.
AU - Atkins, James N.
AU - Crown, John P.
AU - Polikoff, Jonathan
AU - Boileau, Jean Francois
AU - Provencher, Louise
AU - Stokoe, Christopher
AU - Moore, Timothy D.
AU - Robidoux, André
AU - Flynn, Patrick J.
AU - Borges, Virginia F.
AU - Albain, Kathy S.
AU - Swain, Sandra M.
AU - Paik, Soonmyung
AU - Mamounas, Eleftherios P.
AU - Wolmark, Norman
N1 - Funding Information:
Supported by the National Cancer Institute (NCI) Grants No. U10CA180868, U10CA180822, U10CA44066, and UG1-189867; Genentech, a Member of the Roche Group, through the NCI; and through F. Hoffmann-La Roche for Cancer Trials Ireland.
Publisher Copyright:
Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
PY - 2020/2/10
Y1 - 2020/2/10
N2 - PURPOSE: Adjuvant trastuzumab reduces invasive breast cancer (IBC) recurrence and risk for death in patients with HER2-amplified or overexpressing IBC. A subset of patients in the landmark trastuzumab adjuvant trials who originally tested HER2-positive but were HER2-negative by central HER2 testing appeared to possibly benefit from trastuzumab. The objective for the NSABP B-47 trial was to determine whether the addition of trastuzumab to adjuvant chemotherapy (CRx) would improve invasive disease-free survival (IDFS) in patients with HER2-negative breast cancer.PATIENTS AND METHODS: A total of 3,270 women with high-risk primary IBC were randomly assigned to CRx with or without 1 year of trastuzumab. Eligibility criteria included immunohistochemistry (IHC) score 1+ or 2+ with fluorescence in situ hybridization ratio (FISH) < 2.0 or, if ratio was not performed, HER2 gene copy number < 4.0. CRx was either docetaxel plus cyclophosphamide or doxorubicin and cyclophosphamide followed by weekly paclitaxel for 12 weeks.RESULTS: At a median follow-up of 46 months, the addition of trastuzumab to CRx did not improve IDFS (5-year IDFS: 89.8% with CRx plus trastuzumab [CRxT]
v 89.2% with CRx alone; hazard ratio [HR], 0.98; 95% CI, 0.76 to 1.25;
P = .85). These findings did not differ by level of HER2 IHC expression, lymph node involvement, or hormone-receptor status. For distant recurrence-free interval, 5-year estimates were 92.7% with CRxT compared with 93.6% for CRx alone (HR, 1.10; 95% CI, 0.81 to 1.50;
P = .55) and for overall survival (OS) were 94.8% with CRxT and 96.3% in CRx alone (HR, 1.33; 95% CI, 0.90 to 1.95;
P = .15). There were no unexpected toxicities from the addition of trastuzumab to CRx.
CONCLUSION: The addition of trastuzumab to CRx did not improve IDFS, distant recurrence-free interval, or OS in women with non-HER2-overexpressing IBC. Trastuzumab does not benefit women without IHC 3+ or FISH ratio-amplified breast cancer.
AB - PURPOSE: Adjuvant trastuzumab reduces invasive breast cancer (IBC) recurrence and risk for death in patients with HER2-amplified or overexpressing IBC. A subset of patients in the landmark trastuzumab adjuvant trials who originally tested HER2-positive but were HER2-negative by central HER2 testing appeared to possibly benefit from trastuzumab. The objective for the NSABP B-47 trial was to determine whether the addition of trastuzumab to adjuvant chemotherapy (CRx) would improve invasive disease-free survival (IDFS) in patients with HER2-negative breast cancer.PATIENTS AND METHODS: A total of 3,270 women with high-risk primary IBC were randomly assigned to CRx with or without 1 year of trastuzumab. Eligibility criteria included immunohistochemistry (IHC) score 1+ or 2+ with fluorescence in situ hybridization ratio (FISH) < 2.0 or, if ratio was not performed, HER2 gene copy number < 4.0. CRx was either docetaxel plus cyclophosphamide or doxorubicin and cyclophosphamide followed by weekly paclitaxel for 12 weeks.RESULTS: At a median follow-up of 46 months, the addition of trastuzumab to CRx did not improve IDFS (5-year IDFS: 89.8% with CRx plus trastuzumab [CRxT]
v 89.2% with CRx alone; hazard ratio [HR], 0.98; 95% CI, 0.76 to 1.25;
P = .85). These findings did not differ by level of HER2 IHC expression, lymph node involvement, or hormone-receptor status. For distant recurrence-free interval, 5-year estimates were 92.7% with CRxT compared with 93.6% for CRx alone (HR, 1.10; 95% CI, 0.81 to 1.50;
P = .55) and for overall survival (OS) were 94.8% with CRxT and 96.3% in CRx alone (HR, 1.33; 95% CI, 0.90 to 1.95;
P = .15). There were no unexpected toxicities from the addition of trastuzumab to CRx.
CONCLUSION: The addition of trastuzumab to CRx did not improve IDFS, distant recurrence-free interval, or OS in women with non-HER2-overexpressing IBC. Trastuzumab does not benefit women without IHC 3+ or FISH ratio-amplified breast cancer.
KW - Antineoplastic Agents, Immunological/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Breast Neoplasms/drug therapy
KW - Chemotherapy, Adjuvant
KW - Cyclophosphamide/administration & dosage
KW - Disease-Free Survival
KW - Docetaxel/administration & dosage
KW - Doxorubicin/administration & dosage
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - In Situ Hybridization, Fluorescence
KW - Middle Aged
KW - Neoplasm Invasiveness
KW - Receptor, ErbB-2/biosynthesis
KW - Risk Factors
KW - Trastuzumab/administration & dosage
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U2 - 10.1200/JCO.19.01455
DO - 10.1200/JCO.19.01455
M3 - Article
C2 - 31821109
AN - SCOPUS:85079078746
VL - 38
SP - 444
EP - 453
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 5
ER -