Capecitabine vs. capecitabine + trastuzumab in patients with HER2-positive metastatic breast cancer progressing during trastuzumab treatment: The TBP phase III study (GBG 26/BIG 3–05)

Minckwitz, Gϋnter von; Zielinski, C.; Maarteense, E.; Vogel, P.; Schmidt, Maike; Eidtmann, Holger; Čufer, Tanja; Jongh, Felix E. de; Kaufmann, M.; Loibl, Sibylle

doi:10.1200/jco.2008.26.15_suppl.1025

Cited by 61 publications

(35 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These data suggest that enhanced ADCC is unlikely to be the mechanism by which the strongly enhanced activity of trastuzumab and pertuzumab, observed in vivo, is mediated. However, as HER2 overexpression is not lost after treatment with either trastuzumab or pertuzumab, ADCC may still provide a mechanism by which both trastuzumab and pertuzumab can continue to provide an antitumor effect even after progression on trastuzumab, as observed in recent clinical trials (39)(40)(41). These trials and our data suggest that patients who progress on trastuzumab therapy may still benefit from continued trastuzumab and that acquired resistance to trastuzumab is not equivalent to traditional mechanisms of chemotherapy resistance.…”

Section: Discussionsupporting

confidence: 47%

Strongly Enhanced Antitumor Activity of Trastuzumab and Pertuzumab Combination Treatment on HER2-Positive Human Xenograft Tumor Models

et al. 2009

View full text Add to dashboard Cite

The human epidermal growth factor receptor (HER) family plays an important role in cell survival and proliferation, and is implicated in oncogenesis. Overexpression of HER2 is associated with aggressive disease and poor prognosis. Trastuzumab is a humanized monoclonal antibody targeting HER2 and has proven survival benefit for women with HER2-positive early and metastatic breast cancer. Pertuzumab, another monoclonal antibody, is a HER2 dimerization inhibitor that binds to a different epitope on HER2 than trastuzumab and inhibits HER2 dimer formation with other HER family members such as HER3 and HER1. We investigated the antitumor activity of these agents alone and in combination in HER2-positive breast and non-small cell lung cancer xenografts. Our data show that the combination of trastuzumab and pertuzumab has a strongly enhanced antitumor effect and induces tumor regression in both xenograft models, something that cannot be achieved by either monotherapy. The enhanced efficacy of the combination was also observed after tumor progression during trastuzumab monotherapy. Near-IR fluorescence imaging experiments confirm that pertuzumab binding to tumors is not impaired by trastuzumab pretreatment. Furthermore, we show by in vitro assay that both trastuzumab and pertuzumab potently activate antibody-dependent cellular cytotoxicity. However, our data suggest that the strongly enhanced antitumor activity is mainly due to the differing but complementary mechanisms of action of trastuzumab and pertuzumab, namely inhibition of HER2 dimerization and prevention of p95HER2 formation. [Cancer Res 2009;69(24):9330-6]

show abstract

Section: Discussionsupporting

confidence: 47%

Strongly Enhanced Antitumor Activity of Trastuzumab and Pertuzumab Combination Treatment on HER2-Positive Human Xenograft Tumor Models

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In the lapatinib plus capecitabine registration trial, oral lapatinib therapy was maintained until the time of disease progression or based on adverse events [331,332]. In a recent study, a higher efficacy but similar toxicity were found when trastuzumab was continued beyond progression and second-line chemotherapy with capecitabine was initiated [365]. However, there is increasing evidence that continuation of anti-HER-2 therapy after progression on trastuzumab confers clinical benefit.…”

Section: Duration Of Anti-her-2 Targeted Therapymentioning

confidence: 99%

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

et al. 2009

View full text Add to dashboard Cite

1. Contrast the current strengths and limitations of the three main slide-based techniques (IHC, FISH, and CISH) currently in clinical use for testing breast cancer tissues for HER-2 status.2. Compare the efficacy of trastuzumab-and lapatinib-based regimens in the adjuvant and metastatic settings as reported in published clinical trials and regulatory approval databases.3. Contrast the list of biomarkers that have been associated with clinical resistance to trastuzumab and lapatinib and describe their current level of validation.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTThe human epidermal growth factor receptor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. The validation of the general prognostic significance of HER-2 gene amplification and protein overexpression in the absence of anti-HER-2 targeted therapy is discussed in a study of 107 published studies involving 39,730 patients, which produced an overall HER-2-positive rate of 22.2% and a mean relative risk for overall survival (OS) of 2.74. The issue of HER-2 status in primary versus metastatic breast cancer is considered along with a section on the features of metastatic HER-2-positive disease. The major marketed slide-based HER-2 testing approaches, immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ

show abstract

“…88 Furthermore, a prospective randomized study involving 112 patients with MBC showed that trastuzumab plus capecitabine after initial progression during trastuzumab-based therapy achieved better results (PFS, 8.5 months; OS, 20.3 months) than with capecitabine alone (PFS, 5.6 months; OS, 19.9 months). 89 However, further controlled trials are needed to confirm the efficacy of repeated trastuzumab treatment after tumor relapse.…”

mentioning

confidence: 99%

Treatment Options for Breast Cancer Resistant to Anthracycline and Taxane

Moreno-Aspitia

Perez

2009

Mayo Clinic Proceedings

View full text Add to dashboard Cite

Breast cancer is the most common noncutaneous malignancy among every major ethnic group of women in the United States. Anthracyclines and taxanes are the most active and widely used chemotherapeutic agents for breast cancer, but the increased use of these agents at an early stage of disease often renders tumors resistant to these drugs by the time the disease recurs, thereby reducing the number of treatment options for metastatic disease. Moreover, even when these agents can be used in the metastatic setting, treatment failure occurs in most cases, and as a result the 5-year survival rates of patients with metastatic breast cancer are low. This outcome underscores the need for new, effective treatments of metastatic breast cancer and has led to investigation of novel ways to overcome the problem of drug resistance. This article reviews the current treatment options for breast cancer resistant to anthracycline and taxane and provides recommendations for disease management. Published sources for this review were found by searching PubMed (https://www.ncbi.nlm.nih.gov/pubmed) and congress Web sites.Mayo Clin Proc. 2009;84(6):533-545 B reast cancer is the most common noncutaneous malignancy among every major ethnic group of women in the United States, annually causing nearly 40,000 deaths in the United States and more than 400,000 deaths worldwide.1,2 Anthracyclines and taxanes are the most active and widely used chemotherapeutic agents for treating breast cancer in hormone receptor-negative patients and those whose disease progresses while they are taking hormone therapy.3 These agents are commonly used in the adjuvant setting, either in combination or sequentially.4 A metaanalysis of 13 clinical trials involving nearly 23,000 women with high-risk, early-stage breast cancer showed that incorporating taxanes into anthracycline-based regimens significantly improves disease-free survival and overall survival (OS) rates. 5,6 This benefit is evident regardless of hormone receptor status, degree of nodal involvement, age, menopausal status, and type of taxane or administration schedule. Anthracyclines and taxanes, either alone or in combination, are also the preferred option for hormone receptor-negative patients with metastatic breast cancer (MBC). 7 Response rates of 25% to 69% have been reported when taxanes (paclitaxel or docetaxel) are used as ABC = ATP-binding cassette; BCRP = breast cancer resistance protein; CI = confidence interval; EGFR = epidermal growth factor receptor; FDA = Food and Drug Administration; HER2 = human epidermal growth factor receptor 2; IRR = independent radiology review; MBC = metastatic breast cancer; MDR = multidrug resistance protein; NCCN = National Comprehensive Cancer Network; ORR = overall response rate; OS = overall survival; PARP-1 = poly-ADP-ribose polymerase 1; PFS = progression-free survival; TN = triple negative; TTP = time to progression; VEGF = vascular endothelial growth factor

show abstract

Capecitabine vs. capecitabine + trastuzumab in patients with HER2-positive metastatic breast cancer progressing during trastuzumab treatment: The TBP phase III study (GBG 26/BIG 3–05)

Cited by 61 publications

References 0 publications

Strongly Enhanced Antitumor Activity of Trastuzumab and Pertuzumab Combination Treatment on HER2-Positive Human Xenograft Tumor Models

Strongly Enhanced Antitumor Activity of Trastuzumab and Pertuzumab Combination Treatment on HER2-Positive Human Xenograft Tumor Models

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

Treatment Options for Breast Cancer Resistant to Anthracycline and Taxane

Contact Info

Product

Resources

About