Pertuzumab

About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.

Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study

Abstract: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. Patients with stage I–IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40–49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.

Efficacy and Safety of Single-Agent Pertuzumab (rhuMAb 2C4), a Human Epidermal Growth Factor Receptor Dimerization Inhibitor, in Castration-Resistant Prostate Cancer After Progression From Taxane-Based Therapy

Abstract: Purpose Pertuzumab represents a new class of targeted anticancer agents, human epidermal growth factor receptor (HER) dimerization inhibitors. The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent pertuzumab in castration-resistant prostate cancer (CRPC) patients who had experienced progression after prior chemotherapy. Patients and Methods Patients received pertuzumab every 3 weeks. All castration-resistant patients had experienced progression after at least one taxane-based regimen. Patients received a loading dose of 840 mg pertuzumab (cycle 1) followed by 420 mg for subsequent cycles. The primary end point was overall response and safety. A separate retrospective analysis of actual survival time versus predicted survival time for a patient population with comparable prognostic features was performed. Results Patients were enrolled (N = 42) and treated (n = 41). No patients had complete or partial response (as defined by Response Evaluation Criteria in...

Dual Blockade of HER2 in HER2-Overexpressing Tumor Cells Does Not Completely Eliminate HER3 Function

Abstract: Purpose: Dual blockade of HER2 with trastuzumab and lapatinib or with pertuzumab is a superior treatment approach compared with single-agent HER2 inhibitors. However, many HER2-overexpressing breast cancers still escape from this combinatorial approach. Inhibition of HER2 and downstream phosphoinositide 3-kinase (PI3K)/AKT causes a transcriptional and posttranslational upregulation of HER3 which, in turn, counteracts the antitumor action of the HER2-directed therapies. We hypothesized that suppression of HER3 would synergize with dual blockade of HER2 in breast cancer cells sensitive and refractory to HER2 antagonists. Experimental Design: Inhibition of HER2/HER3 in HER2 + breast cancer cell lines was evaluated by Western blotting. We analyzed drug-induced apoptosis and two- and three-dimensional growth in vitro . Growth inhibition of PI3K was examined in vivo in xenografts treated with combinations of trastuzumab, lapatinib, and the HER3-neutralizing monoclonal antibody U3-1287. Results: Treatment with U3-1287 blocked the upregulation of total and phosphorylated HER3 that followed treatment with lapatinib and trastuzumab and, in turn, enhanced the antitumor action of the combination against trastuzumab-sensitive and -resistant cells. Mice bearing HER2 + xenografts treated with lapatinib, trastuzumab, and U3-1287 exhibited fewer recurrences and better survival than mice treated with lapatinib and trastuzumab. Conclusions: Dual blockade of HER2 with trastuzumab and lapatinib does not eliminate the compensatory upregulation of HER3. Therapeutic inhibitors of HER3 should be considered as part of multidrug combinations aimed at completely and rapidly disabling the HER2 network in HER2-overexpressing breast cancers. Clin Cancer Res; 19(3); 610–9. ©2012 AACR .

Neoadjuvant Therapy for HER2-positive Breast Cancer.

Abstract: In HER2-positive early breast cancer, neoadjuvant treatment with a combination of sequential chemotherapy and HER2-targeted therapy is currently the standard of care. This is followed by breast surgery, radiotherapy (if indicated), completion of 12 months of HER2-directed therapy, and - depending on the tumor biology - endocrine adjuvant therapy, and ultimately follow up. 10-year survival rates in the HER2-positive subgroup of breast cancer do reach now more than 75% with the introduction of first adjvuant and later neoadjuvant HER2-targeted therapies over the last 15 years. The neoadjvuant setting helps to downstage locally advanced tumors, to provide early information of tumor response, to assess the efficacy of new therapies in vivo, to reduce treatment duration, and to introduce new targeted therapies into the clinical routine. It also allows enrolling fewer patients into clinical trials in order to reach adequate effects in clinical outcome. The neoadjuvant approach and our interest in this setting are based on pCR (pathological complete response) and its translation into better long-term outcome. In recent trials, we have reached more than 60% pCR with a subsequent improvement of DFS and hopefully OS. Therefore, chemotherapy schedules and new HER2-targeted agents such as lapatinib, pertuzumab, and T-DM1 have been introduced into the neoadjuvant setting. To balance over- and undertreatment, current trials include personalized concepts and assess new biomarkers and tumorbiological factors. We have learned for example to differentiate between HR (hormone receptor)-positive and -negative tumors in the HER2-positive population. Depending on pCR or non-pCR after neoadjuvant treatment, the adjuvant therapy may be adjusted. This concept of post-neo-adjuvant trials is now entering the field of strategies in the neoadjuvant setting for HER2-positive non-metastatic primary breast cancer. The 2017 standard of care in the neoadjuvant setting according to national and international guidelines combines a taxane-containing chemotherapy with a dual blockade of trastuzumab and pertuzumab. This review will point out current trials and their strategies to continue improving outcome and reduce morbidity as well as mortality in HER2-positive early breast cancer.