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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: In this paper, the authors assessed real-world risk of invasive disease recurrence (IDR) and associated factors in patients with human epidermal growth factor receptor-2 positive (HER2+) early breast cancer (BC) with pathological complete responses (pCR) after neoadjuvant pertuzumab plus trastuzumaab (nPT) plus chemotherapy, followed by adjuvant trastusumab (aT), patients with HER2+ BC with pCR after nPT from 2013 to 2015 who received aT were identified in the US Onc
Abstract: This study assessed real-world risk of invasive disease recurrence (IDR) and associated factors in patients with human epidermal growth factor receptor-2 positive (HER2+) early breast cancer (BC) with pathological complete responses (pCR) after neoadjuvant pertuzumab plus trastuzumab (nPT) plus chemotherapy, followed by adjuvant trastuzumab (aT). Patients with HER2+ BC with pCR after nPT from 2013 to 2015 who received aT were identified in the US Oncology Network and followed until IDR or censoring. Kaplan–Meier and Cox regression methods were used to assess invasive disease-free survival (iDFS) and correlation between iDFS and patient characteristics. A total of 217 pCR patients’ charts were reviewed; median age was 52 years. Most had stage IIA or IIB disease (62%), Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1 (84%), tumor size > 2 cm (75%), positive nodes (N+, 62%) and negative estrogen and progesterone receptor (ER− and PR−) expression (52%). Four-year iDFS rates were 90.0% overall (95% CI 84.6%, 93.6%), 86.2% for the N+ cohort and 96.0% for the N− cohort. Cox regression suggested that age, body mass index, ECOG PS, N+ status, stage T3 or T4, and ER+ or PR+ status were risk factors for IDR but were not statistically significant. Consistent with previous studies, this real-world study observed that patients with HER2+ BC showing pCR with nPT remain at risk for IDR, especially with node-positive disease at diagnosis. Alternatives to adjuvant trastuzumab alone, including combined trastuzumab and pertuzumab, should be considered to improve outcomes for initially N+ patients showing pCR with nPT.

9 citations

Journal ArticleDOI
TL;DR: The continuing value of some therapeutic drugs and new agents under development for the treatment of breast cancer, including epidermal growth factor receptor-targeted inhibitor, selective estrogen receptor modulators and aromatase inhibitors, are summarized.
Abstract: Purpose of review This review summarizes the continuing value of some therapeutic drugs and new agents under development for the treatment of breast cancer. Recent findings Overexpression and activation of various growth factor receptors occurs frequently in human breast cancer. Therapeutic approaches mainly involve the epidermal growth factor receptor family, insulin-like growth factor receptor and vascular endothelial growth factor receptor. Therapeutic agents targeting these receptors include the monoclonal antibodies trastuzumab and pertuzumab, and the small-molecule inhibitors gefitinib and erlotinib. Other small-molecule and dual inhibitors are in development, some of which have been demonstrated to have higher efficacy in the treatment of breast cancer. The selective estrogen receptor modulators and aromatase inhibitors continue to be valuable in the endocrine therapy of breast cancer. These drugs have been shown to have higher efficacy than conventional therapy agents, and to have extensive potential, especially in the treatment of postmenopausal women with advanced breast cancer. Summary Approved agents including epidermal growth factor receptor-targeted inhibitor, selective estrogen receptor modulators and aromatase inhibitors continue to be valuable in treating breast cancer. To overcome the acquired resistance caused by these agents and to enhance the therapy effect, the development of new and specific dual inhibitors targeting various growth factor receptors will be important in the future.

9 citations

Proceedings ArticleDOI
TL;DR: A phase 1, first-in-human, single-arm, multi-center, open-label, dose escalation study to assess safety, tolerability, and pharmacokinetics of MP0274 in patients with advanced HER2-positive solid tumors, suggesting it could be a valid treatment option for HER2 positive cancers.
Abstract: Background: MP0274 is a four domain, trispecific, biparatopic, HER2-targeted Designed Ankyrin Repeat Protein (DARPin®) drug candidate. M0274 binds to domains II and IV of HER2 at different sites from trastuzumab and pertuzumab, and to human serum albumin for an extended half-life. MP0274 displays a unique mode of action in preclinical models by directly inducing apoptosis in HER2-addicted cancer cells. Compared to anti-HER2 monoclonal antibodies, preclinical studies revealed no additional safety signals and no maximum tolerated dose was reached. Trial Design: This is a first-in-human study with 2 parts. The dose escalation part of the study, follows a classical 3+3 dose escalation approach, including one extra cycle for exploration of specific PK characteristics, and will establish the recommended dose (RD) for further development based on safety, pharmacokinetics (PK), and preliminary efficacy. The extension part is designed to confirm safety and further estimate efficacy at the RD in additional patients. MP0274 monotherapy will be administered as infusion over one hour every 3 weeks until disease progression. Eligibility Criteria: The study population for this first-in-human study is HER2-positive cancer patients who have progressed after standard therapy for advanced disease. Inclusion/exclusion criteria are similar to those in studies with anti-HER2 antibodies. Specific Aims: The primary objective is to assess safety and tolerability. Secondary objectives are PK, preliminary anti-tumor efficacy (RECIST), and characterization of immunogenicity. Biomarker evaluation include exploratory markers such as PIK3CA, BCL2, p53, PTEN and p21 in both tissue or plasma (ctDNA), investigation of drug induced apoptotic markers as well as additional translational research. This may help get a deeper insight into MP02749s mode of action and into potential resistance mechanisms. MP0274 may have the potential to be active against all HER2-dependent tumors including those that are resistant to trastuzumab and pertuzumab due to incomplete signaling inhibition or inadequate ADCC functionality. MP0274 could be a valid treatment option for HER2 positive cancers. Statistical Methods: Due to being of non-comparative nature, no inferential statistical analysis will be applied in either the escalation or the expansion part of this study. Results will be listed and summarized by dose regimen using descriptive statistics. An interim evaluation of safety, tolerability and preliminary anti-tumor activity will be performed after 14 patients have been dosed at RD at least once and have completed end of Cycle 4. An interim analysis will be performed once all planned 29 patients have been dosed at RD at least once and completed end of Cycle 7 (pre-Cycle 8) tumor assessment. The final statistical analysis will occur after all patients have discontinued treatment for any reason and completed safety follow-up. Present Accrual and target accrual: Currently recruitment is planned in UK, Germany, and Switzerland. Target accrual is 36 evaluable patients. Citation Format: Baird R, Omlin A, Kiemle-Kallee J, Fiedler U, Zitt C, Feurstein D, Herbst J, Dawson K, vom Baur E, Stumpp M, Hermann F, Harstrick A, Schneeweiss A. MP0274-CP101: A phase 1, first-in-human, single-arm, multi-center, open-label, dose escalation study to assess safety, tolerability, and pharmacokinetics of MP0274 in patients with advanced HER2-positive solid tumors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-03-02.

9 citations

Journal ArticleDOI
01 Jul 2017
TL;DR: It is shown that HER2 therapy interruption in patients with metastatic HER2+ breast cancer, who have responded to the therapy, is associated with low risk of rapid disease progression and study suggests that therapy interrupted in cases of response and reinitiation in progression is feasible.
Abstract: Introduction Human epidermal growth factor receptor 2 (HER2)-targeted-therapy regimens can lead to prolonged tumour responses in metastatic HER2+ breast cancer. Clinical trials have concerned use of HER2-targeted agents until disease progression, but it is unknown whether the therapy can be interrupted in cases of a good response. Methods Single institute, retrospective collection of data on patients with HER2+ metastatic breast cancer (n=68) was carried out through a pharmacy search for patients who had received trastuzumab in 2006–2014. Clinical and pathological factors, treatment history and survival data were collected from patient records. Results Median survival in metastatic disease (all patients) was 32 months and survival times were dramatically different in patients with and without trastuzumab as adjuvant or primary metastatic disease (median 16, 77 and 35 months, respectively; p=0.0004). More importantly, HER2 therapy was intentionally interrupted in 21 responding patients, and these patients experienced long HER2-therapy-free intervals (median 51 months), with excellent long-term survival. A lack of previous adjuvant trastuzumab was the only statistically significant factor predictive of HER2 therapy interruption. Conclusions These results from our retrospective study show that HER2 therapy interruption in patients with metastatic HER2+ breast cancer, who have responded to the therapy, is associated with low risk of rapid disease progression. Study suggests that therapy interruption in cases of response and reinitiation in progression is feasible.

9 citations

Journal ArticleDOI
01 Jul 2022-Cancers
TL;DR: The milestones that have had an impact on this disease up to their implementation in clinical practice are intended to understand and the role that modulation of the immune response might play in treatment and prognosis is focused on.
Abstract: Simple Summary The development of several antiHuman Epidermal Growth Factor Receptor 2 (HER2) treatments over the last few years has improved the landscape of HER2-positive breast cancer. Despite this, relapse is still the main issue in HER2-positive breast cancer. The reasons for therapeutic failure lie in the heterogeneity of the disease itself, as well as in the drug resistance mechanisms. In this review, we intended to understand the milestones that have had an impact on this disease up to their implementation in clinical practice. In addition, understanding the underlying molecular biology of HER2-positive disease is essential for the optimization and personalization of the different treatment options. For this reason, we focused on two relevant aspects, which are triple-positive disease and the role that modulation of the immune response might play in treatment and prognosis. Abstract Despite the improvement achieved by the introduction of HER2-targeted therapy, up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown a significant improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). In ER+ HER2+ patients, target therapies such as phosphoinositide-3-kinase (PI3K) pathway inhibition or cyclin-dependent kinases 4/6 blocking may be effective in controlling downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies. Multiple trials have explored these strategies with some promising results, and probably, in the next years conclusive results will succeed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents such as HER-2 therapy plus checkpoint inhibitors, or new vaccines approaches have been investigated in this setting, with promising but controversial results obtained to date.

9 citations


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