Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial

Coudert, Bruno; Arnould́, Laurent; Moreau, L.; Chollet, Philippe; Weber, B.; Vanlemmens, Laurence; Molucon, C.; Tubiana, N.; Causeret, S.; Misset, J.-L.; Feutray, S.; Méry-Mignard, D.; Garnier, J. L.; Fumoleau, P.

doi:10.1093/annonc/mdj096

Cited by 90 publications

(56 citation statements)

References 17 publications

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“…This treatment strategy is associated with a high pathologic response rate (Coudert et al, 2005), which is in accordance with the good efficacy previously reported for the combination of paclitaxel and trastuzumab in this setting (Bines et al, 2003;Burstein et al, 2003;Schiffhauer et al, 2003;Van Pelt et al, 2003;Baselga et al, 2004). In order to discount the effects of intratumoural immune cell modifications that may be induced by conventional chemotherapy drugs, the control group comprised tumours from patients treated with two different PST (Clynes et al, 2000).…”

Section: Discussionsupporting

confidence: 69%

“…These findings may partially explain the synergistic activity of trastuzumab and docetaxel in the treatment of HER2-positive breast cancer and the excellent clinical outcomes afforded by this combination. In the TAXHER01 study (Coudert et al, 2005), tumours that were centrally confirmed to be HER2 positive displayed a pCR of 54%. This is superior to that observed with non-trastuzumab-containing neoadjuvant regimens in unselected patient populations.…”

Section: Discussionmentioning

confidence: 99%

“…This immunohistological analysis, which was undertaken as part of a clinical study, aimed to evaluate the immune response to trastuzumab-based PST within tumours obtained from women with locally advanced breast cancer. breast cancer requiring a mastectomy (but who wished to conserve the breast) were enrolled in the open-label, multicentre, phase II TAXHER01 trial (Coudert et al, 2005). All patients had HER2-positive (immunohistochemistry (IHC) 3 þ or fluorescence in-situ hybridisation (FISH)-positive) breast cancer and were treated with PST consisting of six cycles of docetaxel (100 mg m À2 60-min intravenous (i.v.)…”

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confidence: 99%

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Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?

et al. 2006

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This study evaluated by immunohistochemistry (IHC) immune cell response during neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2-positive primary breast cancer. In all, 23 patients with IHC 3 þ primary breast cancer were treated with trastuzumab plus docetaxel. Pathological complete and partial responses were documented for nine (39%) and 14 (61%) patients, respectively. Case-matched controls comprised patients treated with docetaxel-based PST without trastuzumab (D; n ¼ 23) or PST without docetaxel or trastuzumab (non-taxane, non-trastuzumab, NT -NT; n ¼ 23). All surgical specimens were blind-analysed by two independent pathologists, with immunohistochemical evaluation of B and T lymphocytes, macrophages, dendritic cells and natural killer (NK) cells. Potential cytolytic cells were stained for Granzyme B and TiA1. HER2 expression was also evaluated in residual tumour cells. Trastuzumab treatment was associated with significantly increased numbers of tumour-associated NK cells and increased lymphocyte expression of Granzyme B and TiA1 compared with controls. This study supports an in vivo role for immune (particularly NK cell) responses in the mechanism of trastuzumab action in breast cancer. These results suggest that trastuzumab plus taxanes lead to enhanced NK cell activity, which may partially account for the synergistic activity of trastuzumab and docetaxel in breast cancer.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?

et al. 2006

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“…Neoadjuvant trastuzumab plus chemotherapy demonstrated a significant increase in pCR rates (15.7% vs. 31.7%; P < 0.001). pCR rates with neoadjuvant trastuzumab and anthracycline-free regimens in other studies range from 11% to 76% 22,24,25,[30][31][32][33][34][35] .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline- and nonanthracycline-based regimens for HER2-positive breast cancer.

Bayraktar¹,

González-Angulo²,

Lei³

et al. 2011

JCO

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“…serving surgery or in vivo assessment of tumor response. The addition of trastuzumab to neoadjuvant chemotherapy has shown to significantly increase pCR (pathological Complete Remission), breast sparing surgery and event-free survival in women with operable, HER2-positive disease [17,18]. The phase III randomized study NeoALTTO [19] (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization) was designed to compare the efficacy of neoadjuvant lapatinib, trastuzumab or their combination, in association with paclitaxel.…”

Section: Lapatinib In Combination With Endocrine Agentsmentioning

confidence: 99%

Lapatinib, a TKI Dual Inhibitor of Her1 and Her2 Receptors: Review of the Literature

Lorusso¹,

Marech²,

Giampaglia³

et al. 2012

JCT

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Lapatinib ditosylate (Tyverb ®) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.

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Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial

Abstract: PST with trastuzumab plus docetaxel achieved promising efficacy, with a high pCR rate and good tolerability, in women with stage II or III HER2-positive breast cancer.

Cited by 90 publications

References 17 publications

Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?

Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?

Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline- and nonanthracycline-based regimens for HER2-positive breast cancer.

Lapatinib, a TKI Dual Inhibitor of Her1 and Her2 Receptors: Review of the Literature

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