Trastuzumab plus capecitabine with or without pertuzumab in patients with HER2-positive MBC whose disease has progressed during or following trastuzumab-based therapy for first-line metastatic disease: A multicenter, randomized, two-arm, phase II study (PHEREXA).

Muñoz-Mateu, Montserrat; Urruticoechea, Ander; Šeparović, Robert; Erfán, József; Bachelot, Thomas; Canon, J-L; Коваленко, Н. В.; Starosławska, Elżbieta; Piko, B.; Veyret, Corinne; Pribylova, O.; Ciule, D. L.; Ratnayake, Jayantha; Das, Subhadip; Mayne, Karen; Ross, Gill

doi:10.1200/jco.2011.29.15_suppl.tps118

Cited by 8 publications

(4 citation statements)

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“…22 For example, the PHEREXA study (NCT01026142) is designed to investigate the potential benefit of administering pertuzumab and trastuzmab combined with capecitabine in patients with HER2-positive metastatic breast cancer whose disease has progressed during or following trastuzumab-based therapy for first-line metastatic breast cancer. 23 In this multicenter, openlabel, Phase II trial, patients are randomized 1:1 to receive trastuzumab in combination with capecitabine or trastuzumab, pertuzumab, and capecitabine. Enrollment began in January 2010 and 450 patients will be recruited from ∼130 sites in 19 countries.…”

Section: Ongoing Trials With Pertuzumabmentioning

confidence: 99%

Role of pertuzumab in the treatment of HER2-positive breast cancer

Hubalek

Brantner

Marth

2012

BCTT

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Pertuzumab, a humanized monoclonal antibody to the HER2 receptor, represents a promising new anti-HER2 agent with a novel mechanism of action targeting the inhibition of HER2 dimerization. Nonclinical and clinical data to date indicate that pertuzumab provides a broader HER2 blockade through the inhibition of HER2 heterodimerization. In preclinical experiments, pertuzumab has demonstrated superior antitumor effects when combined with other anti-HER2 treatments such as trastuzumab, compared to when used as monotherapy. Trastuzumab and pertuzumab monoclonal antibodies bind to distinct epitopes on the HER2 receptor without competing with each other, resulting in distinctive mechanisms for disrupting HER2 signaling. These mechanisms are complementary and result in augmented therapeutic efficacy when pertuzumab and trastuzumab are given in combination. Clinically, pertuzumab may have optimal therapeutic effects when given to patients with HER2-positive cancers, in combination with trastuzumab. This observation is supported by recent clinical trials in the metastatic as well as neoadjuvant setting. Intravenous pertuzumab had an acceptable tolerability profile when added to trastuzumab and chemotherapy. This overview will review recent advances in the clinical development of this HER2-targeted therapy.

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Section: Ongoing Trials With Pertuzumabmentioning

confidence: 99%

Role of pertuzumab in the treatment of HER2-positive breast cancer

Hubalek

Brantner

Marth

2012

BCTT

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“…As of the most recent analysis, median OS was 37.6 months for the placebo group and had not yet been reached for the pertuzumab group ( p =0.0008)[83•,84]. Trials evaluating pertuzumab in combination with other agents for first-line and later-line treatment of HER2-positive MBC are ongoing [24–85–87]. Pertuzumab is generally well tolerated, with the most common toxicities including rash, diarrhea, mucositis, and febrile neutropenia when combined with chemotherapy and trastuzumab [88].…”

Section: Fda -Approved Therapy For Her2- Positive Mbcmentioning

confidence: 99%

Therapeutic Considerations When Treating HER2-positive Metastatic Breast Cancer

O’Sullivan

Smith

2014

Curr Breast Cancer Rep

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Despite advances in detection and treatment, metastatic breast cancer (MBC) remains the second highest cause of cancer-related death for women in the United States. Human epidermal growth factor receptor-2 (HER2) is amplified in 25–30% of breast cancers and is associated with aggressive disease and, historically, with poorer outcomes. The advent of trastuzumab, a monoclonal antibody to HER2, revolutionized the management of HER2-positive breast cancer (BC) in the metastatic and adjuvant settings. However, relapse despite adjuvant trastuzumab and resistance to trastuzumab in the metastatic setting remain substantial clinical problems for many patients with HER2-positive BC. As such, analyzing the mechanisms of trastuzumab resistance and developing new therapy to overcome trastuzumab resistance are research priorities. There has been progress, with the approval of three additional HER2-targeted agents in the last six years: lapatinib, pertuzumab, and ado-trastuzumab emtansine (T-DM1). Other HER2-targeted therapies, including neratinib and afatinib, are in clinical development, and trials of novel agents such as heat shock protein-90 (HSP90) inhibitors, phosphatidylinositol-3-kinase (PI3K) inhibitors, and HER2-targeted vaccines are ongoing. In addition to developing new therapy, research is addressing several unique challenges in the management of HER2-positive MBC. In this article, we discuss advances in the treatment of HER2-positive MBC, with a focus on novel HER2-targeted therapy and HER2-targeted agents recently approved by the United States Food and Drug Administration (FDA). Additionally, we also address the management of brain metastases (BM) and hormone receptor (HR) - positive, HER2-positive MBC.

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“…El trastuzumab es incapaz de bloquear el dímero Her2/Her3; en cambio, el pertuzumab se une a un bolsillo del dominio extracelular del Her2 necesario para la dimerización, impidiéndola y reduciendo la activación de la vía PI3K/AKT. Se ha demostrado sinergismo con el trastuzumab tanto en ensayos preclínicos como clínicos 76,77 .…”

Section: B Familia Her: Egfr Y Her3unclassified

Mecanismos de resistencia al trastuzumab

Korbenfeld¹

2012

RevOnco

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El trastuzumab es un anticuerpo monoclonal dirigido contra el receptor del factor de crecimiento epidérmico humano (Her2), el cual se encuentra sobreexpresado en aproximadamente el 20% del cáncer de mama invasivo. El trastuzumab es un claro ejemplo de exitoso desarrollo de terapia “blanco específica” en oncología y actualmente se encuentra aprobado para su uso terapéutico en cáncer de mama Her2+ tanto en enfermedad avanzada como con criterio adyuvante. Sin embargo, alrededor del 50% de las pacientes con cáncer de mama Her2+ no se benefician de las terapias basadas en trastuzumab. El entendimiento de los mecanismos de acción y de resistencia al trastuzumab es crucial para el desarrollo de nuevas estrategias de tratamiento. Los mecanismos de resistencia al trastuzumab se pueden agrupar en 4 categorías principales: A. Obstáculos para la unión del trastuzumab al dominio extracelular del Her2. B. Activación de las vías de traducción de señales río abajo del Her2. C. Activación de vías alternativas del Her2. D. Fallas del sistema inmunitario para destruir las células tumorales. Esta revisión resume las evidencias preclínicas y clínicas acerca de los mecanismos de acción y resistencia al trastuzumab y también discute el desarrollo de nuevas drogas antiHer2 y sus posibles implicancias clínicas.

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Trastuzumab plus capecitabine with or without pertuzumab in patients with HER2-positive MBC whose disease has progressed during or following trastuzumab-based therapy for first-line metastatic disease: A multicenter, randomized, two-arm, phase II study (PHEREXA).

Cited by 8 publications

References 0 publications

Role of pertuzumab in the treatment of HER2-positive breast cancer

Role of pertuzumab in the treatment of HER2-positive breast cancer

Therapeutic Considerations When Treating HER2-positive Metastatic Breast Cancer

Mecanismos de resistencia al trastuzumab

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