Adjuvant trastuzumab in HER2-positive breast cancer.
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trialMartin, M.; Holmes, F.; Ejlertsen, B.; Delaloge, S.; Moy, B.; Iwata, H.; von Minckwitz, G.; Chia, S.; Mansi, J.; Barrios, C.; Gnant, M.; Tomaševic, Z.; Denduluri, N.; Šeparovic, R.; Gokmen, E.; Bashford, A.; Ruiz Borrego, M.; Kim, S.; Jakobsen, E.; Ciceniene, A.; Inoue, K.; Overkamp, F.; Heijns, J.; Armstrong, A.; Link, J.; Joy, A.; Bryce, R.; Wong, A.; Moran, S.; Yao, B.; Xu, F.; Auerbach, A.; Buyse, M.; Chan, Arlene; ExteNET Study Group (2017)Background: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with ...
Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trialChan, Arlene; Delaloge, S.; Holmes, F.; Moy, B.; Iwata, H.; Harvey, V.; Robert, N.; Silovski, T.; Gokmen, E.; von Minckwitz, G.; Ejlertsen, B.; Chia, S.; Mansi, J.; Barrios, C.; Gnant, M.; Buyse, M.; Gore, I.; Smith, J.; Harker, G.; Masuda, N.; Petrakova, K.; Zotano, A.; Iannotti, N.; Rodriguez, G.; Tassone, P.; Wong, A.; Bryce, R.; Ye, Y.; Yao, B.; Martin, M. (2016)Background: Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of ...
Phase II study of a triple combination of oral vinorelbine, capecitabine and trastuzumab as first-line treatment in HER2-positive metastatic breast cancerChan, Arlene; Conte, P.; Petruzelka, L.; Tubiana-Mathieu, N.; Ganju, V.; Llombart, A.; Espie, M.; Majois, F.; Gil, M.; Vaissiere, N.; Villanova, G. (2013)Chemotherapy plus trastuzumab is the standard first-line treatment for Human Epidermal Receptor 2-positive (HER2-positive) metastatic breast cancer. The aim of this international phase II trial was to determine the efficacy ...