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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: Treatment with pertuzumab, trastuzumabs, and docetaxel resulted in a statistically significant improvement in the total pathologic complete response rate vs placebo, trASTuzumAB, andDocetaxe for the neoadjuvant treatment of ERBB2-positive early or locally advanced breast cancer in Asian patients.
Abstract: Importance Prospective assessment of treatments known to benefit patients in global clinical trials in specific racial groups is essential. Objective To compare the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer. Design, Setting, and Participants This multicenter, double-blind, placebo-controlled phase 3 trial enrolled 329 women with ERBB2-positive early (T2-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) and primary tumor larger than 2 cm from March 14, 2016, to March 13, 2017. Analysis of the primary end point was performed on an intention-to-treat basis. Interventions Before surgery, patients received 4 cycles of intravenous pertuzumab (840-mg loading dose and 420-mg maintenance doses), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), and docetaxel (75 mg/m2) or intravenous placebo, trastuzumab, and docetaxel every 3 weeks. After surgery, patients received 3 cycles of intravenous fluorouracil, epirubicin, and cyclophosphamide followed by 13 cycles of the same intravenous anti-ERBB2 therapy (pertuzumab and trastuzumab or placebo and trastuzumab) for up to 1 year. Main Outcomes and Measures The primary end point was independent review committee–assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by disease category and hormone receptor status, was used to compare rates between treatment groups. Results In total, 329 female patients were randomized (pertuzumab, 219; and placebo, 110; mean [SD] age, 48.8 [9.5] years). In the intention-to-treat population, total pathologic complete response rates were 39.3% (86 of 219) in the pertuzumab group and 21.8% (24 of 110) in the placebo group (difference, 17.5% [95% CI, 6.9%-28.0%];P = .001). Of the most common grade 3 or higher adverse events, there was a higher incidence of neutropenia in the pertuzumab group (83 of 218 [38.1%] vs 36 of 110 [32.7%]). Serious adverse events were reported in 10.1% of patients (22 of 218) in the pertuzumab group and 8.2% of patients (9 of 110) in the placebo group. Conclusions and Relevance Treatment with pertuzumab, trastuzumab, and docetaxel resulted in a statistically significant improvement in the total pathologic complete response rate vs placebo, trastuzumab, and docetaxel for the neoadjuvant treatment of ERBB2-positive early or locally advanced breast cancer in Asian patients. Safety data were in line with the known pertuzumab safety profile and generally comparable between treatment groups. The PEONY trial adds to the totality of data showing the benefit of the pertuzumab regimen. Trial Registration ClinicalTrials.gov identifier:NCT02586025

78 citations

Journal ArticleDOI
TL;DR: Clinical success in the metastatic setting provided the rationale for assessing trastuzumab in early breast cancer and four large trials of adjuvant trasts demonstrated significant improvements in disease-free survival and overall survival despite tumor size, nodal or hormone-receptor status, and age.
Abstract: Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression occurs in 20% to 25% of breast tumors, often leading to an aggressive disease course and poor clinical outcomes. Successful targeting of HER2-positive tumors in preclinical models with trastuzumab has translated to the clinic. In HER2-positive metastatic breast cancer (MBC), trastuzumab provides significant clinical benefit as a monotherapy and in combination with numerous chemotherapies. In the phase III trial of first-line trastuzumab plus chemotherapy, overall response rate (ORR; 50%, P < 0.001), overall survival (25.1 months vs. 20.3 months, P = 0.046) and time to disease progression improved significantly compared with chemotherapy alone (7.4 vs. 4.6 months, P < 0.001), and second-line trastuzumab use after prior trastuzumab has resulted in ORRs of up to 50%. Clinical success in the metastatic setting provided the rationale for assessing trastuzumab in early breast cancer. Four large trials of adjuvant trastuzumab demonstrated significant improvements in disease-free survival (33%-52%) and overall survival (34%-41%) despite tumor size, nodal or hormone-receptor status, and age. New approaches to maximize the clinical benefit of trastuzumab-based therapy are under investigation and include novel combinations with other targeted therapies such as bevacizumab, pertuzumab, and lapatinib.

78 citations

Journal ArticleDOI
TL;DR: The TUXEDO-1 trial as discussed by the authors showed that trastuzumab deruxtecan showed a high intracranial response rate in patients with active brain metastases from HER2-positive breast cancer and should be considered as a treatment option in this setting.
Abstract: Abstract Trastuzumab deruxtecan is an antibody–drug conjugate with high extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. We enrolled patients aged ≥18 years with HER2-positive breast cancer and newly diagnosed untreated brain metastases or brain metastases progressing after previous local therapy, previous exposure to trastuzumab and pertuzumab and no indication for immediate local therapy. Patients received trastuzumab deruxtecan intravenously at the standard dose of 5.4 mg per kg bodyweight once every 3 weeks. The primary endpoint was intracranial response rate measured according to the response assessment in neuro-oncology brain metastases criteria. A Simon two-stage design was used to compare a null hypothesis of <26% response rate against an alternative of 61%. Fifteen patients were enrolled in the intention-to-treat population of patients who received at least one dose of study drug. Two patients (13.3%) had a complete intracranial response, nine (60%) had a partial intracranial response and three (20%) had stable disease as the best intracranial response, with a best overall intracranial response rate of 73.3% (95% confidential interval 48.1–89.1%), thus meeting the predefined primary outcome. No new safety signals were observed and global quality-of-life and cognitive functioning were maintained over the treatment duration. In the TUXEDO-1 trial (NCT04752059, EudraCT 2020-000981-41), trastuzumab deruxtecan showed a high intracranial response rate in patients with active brain metastases from HER2-positive breast cancer and should be considered as a treatment option in this setting.

78 citations

Journal ArticleDOI
TL;DR: In this article, a time-resolved fluorescence resonance energy transfer (TR-FRET) method was proposed to quantify EGFR/HER2 heterodimers on cell surface to shed some light on the mechanism of such therapies.

77 citations

01 Mar 2014
TL;DR: The results indicate that HER2/neu overexpression occurred in 14% of the advanced gallbladder cancer cases, which indicates that this subgroup of patients may benefit from inhibitors of the HER2-neu pathway.
Abstract: Background The HER2/neu gene is a proto-oncogene that can predict the response to treatment with trastuzumab, pertuzumab, and lapatinib. This study was conducted to determine the frequency of HER2/neu overexpression and to identify a subgroup of patients with gallbladder cancer who would benefit from targeted therapy. Methods Patients with gallbladder cancer (n = 187; 165 women and 22 men) with a recorded follow-up of at least 5 years were included, along with control subjects (n = 75). An automated immunohistochemical technique was used with an anti-ErbB2 antibody. Scoring was conducted according to the CAP/ASCO (College of American Pathologists/American Society of Clinical Oncology) criteria for breast cancer. Results Overexpression of HER2/neu was observed in 12.8% of the cases. Of those, 0% were mucosal, 14.3% muscular, 12.8% subserosal, and 10.6% serosal. In 20% of the cases, equivocal staining was observed. Overexpression was more frequent in the advanced cancers and in the better differentiated tumors (13.8% and 17.4%, respectively), but the difference was nonsignificant. The patients with overexpression of HER2/neu had a worse overall survival, when compared with those who had no expression at 5 years (34% vs. 41%). Conclusion This is the single largest study of HER2/neu expression in gallbladder cancer to use commonly accepted scoring criteria. The results indicate that HER2/neu overexpression occurred in 14% of the advanced gallbladder cancer cases. This subgroup may benefit from inhibitors of the HER2/neu pathway.

77 citations


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