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

Autor: Jean Francois Boileau, Virginia F. Borges, Kathy S. Albain, Timothy David Moore, Norman Wolmark, André Robidoux, James N. Atkins, Eleftherios P. Mamounas, Reena S. Cecchini, Sandra M. Swain, Patrick J. Flynn, Joseph P. Costantino, Louise Provencher, Charles E. Geyer, Christopher Stokoe, Louis Fehrenbacher, Priya Rastogi, Soonmyung Paik, John Crown, Jonathan Polikoff
Rok vydání: 2019
Předmět:
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Adjuvant chemotherapy
Receptor
ErbB-2
medicine.medical_treatment
Breast Neoplasms
Docetaxel
Disease-Free Survival
law.invention
03 medical and health sciences
0302 clinical medicine
Breast cancer
Antineoplastic Agents
Immunological
Randomized controlled trial
Trastuzumab
law
Risk Factors
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Medicine
Humans
Neoplasm Invasiveness
skin and connective tissue diseases
neoplasms
Cyclophosphamide
In Situ Hybridization
Fluorescence
Chemotherapy
business.industry
ORIGINAL REPORTS
Middle Aged
medicine.disease
Immunohistochemistry
Clinical trial
030104 developmental biology
Chemotherapy
Adjuvant
Doxorubicin
030220 oncology & carcinogenesis
Female
business
Adjuvant
medicine.drug
Zdroj: J Clin Oncol
ISSN: 1527-7755
Popis: 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.
Databáze: OpenAIRE
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