A phase II trial of dasatinib (D) in combination with trastuzumab (T) and paclitaxel (P) in the first line treatment of HER2 positive metastatic breast cancer (MBC) patients (pts): GEICAM/2010-04

Fernández, Antonio; Ruíz-Borrego, Manuel; Martin, M.; Antolín, Silvia; Atienza, M.; Montaño, Álvaro; Ribelles, Nuria; Guerrero, Antonio; Muñoz, M.; Fernández-Pérez, Isaura; Urruticoechea, Ander; González, Alejandro Falcón; Simon, S. Pernas; Varela, J. Prato; Escudero, M.J.; Benito, Sara; Caballero, Rosalía; Carrasco, Eva; Rojo, Federico; Pandiella, Atanasio

doi:10.1093/annonc/mdx365.002

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“…Overall, the clinical trial data using Src inhibitors in unselected metastatic breast cancer patients has been disappointing ( Table 1), but a recent study using Src inhibition in combination with chemotherapy and trastuzumab was more promising and reached an objective response rate of 79% (19). Src activation has been found to be a mechanism of resistance in HER2+ breast cancer (20), and perhaps the combination of Src inhibitors and HER2targeting therapies is a more promising paradigm.…”

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confidence: 99%

Dasatinib in breast cancer: Src-ing for response in all the wrong kinases

Kennedy¹,

Gadi²

2018

Ann. Transl. Med

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mentioning

confidence: 99%

Dasatinib in breast cancer: Src-ing for response in all the wrong kinases

Kennedy¹,

Gadi²

2018

Ann. Transl. Med

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“…Preclinical data suggest trastuzumab-resistant HER2Δ16 cells are sensitive to the SRC kinase inhibitor dasatinib and data from a phase I/II (GEICAM/2010-04) study suggest there may be a signal for activity when dasatinib is combined with trastuzumab and paclitaxel in the first-line treatment for patients with advanced HER2positive breast cancer. 30,31 In addition, SRC activation by itself has been associated with trastuzumab resistance. 32 The mechanisms that contribute to T-DM1 resistance are not fully understood.…”

Section: Mechanisms Of Resistance and Response Heterogeneity To Anti-...mentioning

confidence: 99%

HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance

2019

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The introduction of anti-HER2 therapies to the treatment of patients with HER2-positive breast cancer has led to dramatic improvements in survival in both early and advanced settings. Despite this breakthrough, nearly all patients with metastatic HER2-positive breast cancer eventually progress on anti-HER2 therapy due to de novo or acquired resistance. A better understanding not only of the underlying mechanisms of HER2 therapy resistance but of tumor heterogeneity as well as the host and tumor microenvironment is essential for the development of new strategies to further improve patient outcomes. One strategy has focused on inhibiting the HER2 signaling pathway more effectively with dual-blockade approaches and developing improved anti-HER2 therapies like antibody–drug conjugates, new anti-HER2 antibodies, bispecific antibodies, or novel tyrosine kinase inhibitors that might replace or be used in addition to some of the current anti-HER2 treatments. Combinations of anti-HER2 therapy with other agents like immune checkpoint inhibitors, CDK4/6 inhibitors, and PI3K/AKT/mTOR inhibitors are also being extensively evaluated in clinical trials. These add-on strategies of combining optimized targeted therapies could potentially improve outcomes for patients with HER2-positive breast cancer but may also allow de-escalation of treatment in some patients, potentially sparing some from unnecessary treatments, and their related toxicities and costs.

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A phase II trial of dasatinib (D) in combination with trastuzumab (T) and paclitaxel (P) in the first line treatment of HER2 positive metastatic breast cancer (MBC) patients (pts): GEICAM/2010-04

Cited by 2 publications

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Dasatinib in breast cancer: Src-ing for response in all the wrong kinases

Dasatinib in breast cancer: Src-ing for response in all the wrong kinases

HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance

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