Adjuvant Trastuzumab in HER2-Positive Breast Cancer

Jonsson Comprehensive Cancer Center, University of California–Los Angeles, Los Angeles, CA 90095-1678, USA.
New England Journal of Medicine (Impact Factor: 55.87). 10/2011; 365(14):1273-83. DOI: 10.1056/NEJMoa0910383
Source: PubMed


Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.
We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.
At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.
The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 number, NCT00021255.).

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Available from: Marc Buyse, Jan 12, 2014
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    • "Patients with HER2+ subtypes have higher rates of metastasis and, thus, have lower rates of survival than patients with the less severe luminal A and B subtypes[4]. However, as treatment regimens with trastuzumab have become more standardized, five-year survival rates have increased to 92%[5]. Surgical treatment followed by radiotherapy for single metastatic lesions to the brain can significantly improve overall survival compared to radiosurgery alone67. "

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    • "For example, data from the Cancer Research Network found 5‐year combined HF/CM rates of 12.1% for patients treated with trastuzumab alone, and 20.1% for patients treated with trastuzumab and anthracyclines.(2012) The likely explanation for this difference is that clinical trials typically enrolled younger and healthier subjects, while excluding older patients or those with existing heart disease or cardiac risk factors such as uncontrolled hypertension.(2011) Because women older than 65 years comprise nearly 40% of all breast cancer patients,(2012) estimates of cardiac risk from clinical trials may not necessarily be appropriate for many patients in the general population. "
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    • "Gene expression studies have confirmed the existence of at least four distinct and reproducible breast cancer subtypes with molecular differences based on these markers (Perou et al. 2000). These differences have resulted in stratification in the clinical setting with varying treatment algorithms based on subtype (Paik et al. 2006, Slamon et al. 2011). "
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