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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.


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Journal ArticleDOI
TL;DR: It was revealed that all peptides mimic pertuzumab performance since they exhibit noticeable binding interaction energies, inhibitory efficiencies and number of hot spots, however, YNDSTHGERL with five hot spots and considerable interaction energy has the highest ability in interfering with HER-2-specific epitope.
Abstract: An in silico peptide design strategy is conducted in order to introduce a novel series of pertuzumab mimetic peptides, aimed to target the extracellular domain of HER-2 and prevent its signal transduction. A combination of alanine scanning and contact surface analysis is employed to assess the pertuzumab paratope, HER-2 epitope and their hot spots. Furthermore, the recognised residues are utilised to construct nine 10-mer peptides. Some of the peptides are modified pertuzumab paratope sequences, whereas the others are designed and modified as strongly binding complementary peptides for HER-2 epitope. Evaluation of the peptides is carried out through homology modelling, molecular dynamics simulation (MDS) and docking. It was revealed that all peptides mimic pertuzumab performance since they exhibit noticeable binding interaction energies, inhibitory efficiencies and number of hot spots. However, YNDSTHGERL with five hot spots and considerable interaction energy has the highest ability in interfering with H...

3 citations

Journal ArticleDOI
TL;DR: A phase II study of eribulin mesylate, which extends survival in metastatic breast cancer, with trastuzumab-pertuzumaab (HP) in patients with previously treated HER2+ MBC was conducted in this article.
Abstract: There are limited data on trastuzumab–pertuzumab (HP)-based treatments beyond the first-line, HER2+ metastatic breast cancer (MBC) setting. We conducted a phase II study of eribulin mesylate, which extends survival in MBC, with HP in patients with previously treated HER2+ MBC to evaluate efficacy, toxicity, and genomic alterations driving therapeutic response. After a run-in phase for eribulin dosing, two cohorts were enrolled (Cohort A-no prior pertuzumab; Cohort B-prior pertuzumab). All patients received eribulin 1.4 mg/m2 on days 1, 8 with standard-dose HP on day 1 (21-day cycles). The primary endpoint was objective response rate (ORR). Genomic characterization via whole exome sequencing (WES) was completed on tumor DNA and matched germline DNA from 19 patients. The six-patient run-in established a dose of eribulin 1.4 mg/m2 with HP. Cohorts A and B enrolled 17 and 7 patients, respectively. Accrual stopped early due to an evolving treatment landscape and slow enrollment. The ORR was 26.3% (95% Confidence Interval [CI] 9.2–51.2%) in Cohort A and 0% in Cohort B (95% CI 0–41.0%). WES revealed more frequent alterations in TP53 (p 0.05) in patients without clinical benefit (disease control for < 24 weeks) which was not significant after multiple hypothesis correction. Eribulin–HP had manageable toxicity and modest clinical activity in patients without prior pertuzumab exposure. This study provides a preliminary landscape of somatic alterations in this patient cohort. Our data add to the literature on how genomic alterations may predict for therapy response/resistance, as we work to individualize choices in a quickly evolving HER2+ MBC treatment landscape. www.clinicaltrials.gov , NCT01912963. Registered 24 July 2013.

3 citations

Journal ArticleDOI
15 Apr 2014
TL;DR: T-DM1 was well tolerated in Japanese patients; however, the incidence of grade 3 or 4 thrombocytopenia was higher than that observed in earlier western studies, but was not associated with clinically important symptoms.
Abstract: Anti-HER2 agents, such as trastuzumab, lapatinib, trastuzumab emtansine (T-DM1), and pertuzumab, are standard agents in the treatment of breast cancer overexpressing the human epidermal growth factor receptor 2 (HER2). Trastuzumab is the first approved HER2-targeted agent. Subsequent developments include agents with different mechanisms. In this paper, we review the results of clinical trials of T-DM1, a new anti-HER2 agent, with a focus on Japanese patients with breast cancer. On the basis of results from a Phase I study (JO22591), the maximum tolerated dose was determined to be 3.6 mg/kg every 3 weeks for both Japanese and western patients. In a Phase II study (JO22997), the overall response rate was 38.4% (90% confidence interval 28.8-48.6). T-DM1 was well tolerated in Japanese patients; however, the incidence of grade 3 or 4 thrombocytopenia was higher than that observed in earlier western studies, but was not associated with clinically important symptoms. Pharmacokinetic parameters for T-DM1 and its metabolites were consistent with those reported previously from a Phase I or II study in non-Japanese patients, and the data obtained showed no suggestion of ethnic differences. Several Phase III studies of T-DM1 are ongoing throughout the world, including in Japanese patients with breast cancer.

3 citations

Proceedings ArticleDOI
TL;DR: Cardiac and general safety of the two anthracycline-containing regimens in BERENICE were as expected and were consistent with the known P+H+CT profiles; both regimens were active, and tpCR rates were high.
Abstract: Background: Neoadjuvant pertuzumab (P)+trastuzumab (H)+standard chemotherapy (CT) significantly increases pathologic complete response (pCR) rates v H+CT. However, anti-HER2 therapy following anthracyclines can cause heart failure, and data are limited or lacking on combining P+H after epirubicin or doxorubicin. We report cardiac and overall safety as well as total pCR (tpCR) rates with widely used but understudied anthracycline-containing regimens. Methods: BERENICE (NCT02132949), a non-randomized, open-label, phase II study, enrolled patients (pts) with centrally confirmed HER2-positive, locally advanced, inflammatory, or early-stage, unilateral, and invasive breast cancer, Eastern Cooperative Oncology Group performance status ≤1, and baseline left ventricular ejection fraction (LVEF) ≥55%. In the neoadjuvant period, Cohort A pts received four q2w dose-dense doxorubicin+cyclophosphamide cycles (60 mg/m2/600 mg/m2 with granulocyte-colony stimulating factor support as needed) followed by 12 qw paclitaxel doses (80 mg/m2) + four q3w P+H cycles (P 840 mg, then 420 mg; H 8mg/kg, then 6 mg/kg). Cohort B received four q3w fluorouracil/epirubicin/cyclophosphamide cycles (500 mg/m2/100 mg/m2/600 mg/m2) followed by four q3w docetaxel cycles (75 mg/m2 escalated to 100 mg/m2) + four q3w P+H cycles. Surgery was performed after cycle 8 for both cohorts. The primary objective was to evaluate cardiac safety during the neoadjuvant period, assessed by incidence of 1) New York Heart Association (NYHA) Class III/IV heart failure and 2) significant LVEF declines (≥10% from baseline with a value of Results: Four hundred one pts were enrolled between Jul 2014–Aug 2015. Clinical cutoff was Mar 3, 2016. Demographics and baseline characteristics were generally balanced between cohorts; 64.3% v 61.7% of pts had centrally confirmed hormone receptor (HR)-positive disease and 95.0% v 93.0% had T1–T3 primary tumors. Three pts in Cohort A and none in Cohort B experienced NYHA Class III/IV heart failure during neoadjuvant treatment (table). Thirteen pts in Cohort A v four in Cohort B had significant LVEF declines (table). One Cohort B pt9s LVEF decline was prior to anti-HER2 treatment. AE and serious AE (SAE) rates were well balanced between cohorts. The most common AEs were nausea, diarrhea, and alopecia. The most common SAE was febrile neutropenia. tpCR rates were similar between cohorts (table). Conclusion: Cardiac and general safety of the two anthracycline-containing regimens in BERENICE were as expected and were consistent with the known P+H+CT profiles. Both regimens were active, and tpCR rates were high. Citation Format: Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Eng-Wong J, Dang C. Primary analysis of BERENICE: A phase II cardiac safety study of pertuzumab, trastuzumab, and neoadjuvant anthracycline-based chemotherapy in patients with locally advanced, inflammatory, or early-stage, unilateral, and invasive HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-41.

3 citations

Journal ArticleDOI
23 Jan 2021
TL;DR: In this article, the authors evaluated the cost effectiveness of the combination of pertuzumab, trastuzumaab, and docetaxel for the treatment of patients with human epidermal growth factor receptor-2 (HER2)-positive breast cancer in Japan.
Abstract: The purpose of this analysis was to evaluate the cost effectiveness of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for the treatment of patients with human epidermal growth factor receptor-2 (HER2)-positive breast cancer in Japan. A partitioned survival analysis model was developed to predict costs and quality-adjusted life-years (QALYs) in a PTD arm and a trastuzumab plus docetaxel (TD) arm. Direct medical costs were considered from the perspective of the Japanese healthcare system. The time horizon of the model was set to 20 years. Data on overall survival and progression-free survival were derived from the CLEOPATRA trial. Cost parameters were estimated using a real-world claims database. Utilities were derived from published sources outside Japan. The incremental cost-effectiveness ratio (ICER) of PTD therapy compared with TD therapy was estimated. Sensitivity analysis was conducted to assess the uncertainty in parameter settings. Compared with TD therapy, PTD therapy incurred an additional cost of $US174,479 and conferred an additional 0.949 QALYs. This resulted in an ICER of $US183,901 per QALY gained. Utility weights for progression-free survival and progressed disease had a relatively large impact on the base-case result, but the ICERs remained higher than $US75,000 per QALY over the full range of model parameters. Based on a probabilistic sensitivity analysis, the probability that PTD is cost effective was estimated to be 3.3%. Applying a willingness-to-pay threshold of $US75,000 per QALY, PTD therapy as first-line therapy would not be cost effective. Further research is required on utilities and clinical benefits for Japanese patients with breast cancer.

3 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023372
2022307
2021158
2020144
2019143
2018130