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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: Pertuzumab (Perjeta), a monoclonal antibody against the HER2 dimerization domain, has also been associated with improved patient outcomes in clinical trials, and has recently been approved in combination with chemotherapy and trastuzumAB for neoadjuvant therapy of early stage, HER2-positive breast cancer and first-line treatment of metastatic disease.
Abstract: In the absence of specific therapy, the 15%-20% of breast cancers demonstrating human epidermal growth-factor receptor 2 (HER2) protein overexpression and/or gene amplification are characterized by a more aggressive phenotype and poorer prognosis compared to their HER2-negative counterparts. Trastuzumab (Herceptin), the first anti-HER2-targeted therapy, has been associated with improved survival outcomes in HER2-positive breast cancer. However, many patients with early stage disease continue to relapse, and metastatic disease remains incurable. In order to further improve these outcomes, several novel HER2-targeted agents have recently been developed. Pertuzumab (Perjeta), a monoclonal antibody against the HER2 dimerization domain, has also been associated with improved patient outcomes in clinical trials, and has recently been approved in combination with chemotherapy and trastuzumab for neoadjuvant therapy of early stage, HER2-positive breast cancer and first-line treatment of metastatic disease. This review briefly summarizes pertuzumab's clinical development as well as the published evidence supporting its use, and highlights some of the currently unanswered questions that will influence pertuzumab's incorporation into clinical practice.

6 citations

Journal ArticleDOI
TL;DR: In this paper, a bispecific anti-HER2 antibody (BsAb) was developed for the treatment of HER2-overexpressing breast cancer using dual variable domain immunoglobulin (DVD-Ig).
Abstract: Overexpression of HER2 has been reported in many types of cancer, making it a perfect candidate for targeted immunotherapy. The combination of two FDA approved monoclonal antibodies (mAbs), trastuzumab and pertuzumab, has more robust anti-tumor activity in patients with HER2-overexpressing breast cancer. We recently produced a new humanized anti-HER2 mAb, hersintuzumab, which recognizes a different epitope than trastuzumab and pertuzumab on HER2. This mAb, in combination with trastuzumab, exhibits more potent anti-tumor activity than each parental mAb alone. Here we have developed a novel bispecific anti-HER2 antibody (BsAb) designated as trasintuzumab, composed of trastuzumab and hersintuzumab, using dual variable domain immunoglobulin (DVD-Ig) technology. Both variable domains of trasintuzumab are fully functional and have similar affinities to the parental mAbs and are also able to bind to natural HER2 on the surface of several HER2-expressing cell lines. Trasintuzumab was found to inhibit the growth of different types of tumor cell lines through suppression of the AKT and ERK signaling pathways as efficiently as the combination of the parental mAbs. It also induced tumor regression as potently as the combination of the two mAbs in nude mice bearing ovarian and gastric cancer xenografts. Our data suggest that trasintuzumab may be a promising BsAb therapeutic candidate for the treatment of HER2-overexpressing cancers.

6 citations

Journal ArticleDOI
TL;DR: During chemotherapy with anti-HER2 therapy, the breast cancer shrank quickly, while the left breast lump suddenly enlarged, resulting in a remission in the 47-year-old Japanese woman.

6 citations

Journal ArticleDOI
TL;DR: Results from this subgroup analysis of the JACOB trial suggest similar efficacy of pertuzumab in Japanese patients and patients in the overall population, encouraging continued investigation of new agents for gastric cancer inJapanese patients.
Abstract: The phase III JACOB trial (NCT01774786) compared the efficacy and safety of pertuzumab and trastuzumab plus chemotherapy with placebo and trastuzumab plus chemotherapy in patients with previously untreated human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric or gastroesophageal junction cancer. We conducted a subgroup analysis in Japanese patients. Patients were randomized 1:1 to pertuzumab 840 mg or placebo, plus trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) and chemotherapy (cisplatin 80 mg/m2, and capecitabine 1000 mg/m2 twice daily for 28 doses or 5-fluorouracil 800 mg/m2 every 24 h for 120 h), every 3 weeks. Continuation of chemotherapy after 6 cycles was at the discretion of the patient and the treating physician. A total of 40 Japanese patients were included in each arm. Median overall survival was 22.0 months (95% confidence interval [CI] 13.8–not evaluable) and 15.6 months (95% CI 9.7–19.2) in the pertuzumab and placebo arms, respectively (hazard ratio [HR] 0.64 [95% CI 0.37–1.10]). Median progression-free survival was 12.4 months (95% CI 6.1–14.1) in the pertuzumab arm and 6.3 months (95% CI 4.3–8.1) in the placebo arm (HR 0.50 [95% CI 0.30–0.82]). Grade ≥ 3 adverse events and serious adverse events were more frequent in the pertuzumab arm than the placebo arm. Results from this subgroup analysis of the JACOB trial suggest similar efficacy of pertuzumab in Japanese patients and patients in the overall population, encouraging continued investigation of new agents for gastric cancer in Japanese patients.

6 citations

Book ChapterDOI
01 Jan 2013
TL;DR: This chapter takes a look at the progress of treatment options in HER2 overexpressing breast cancers with focus on mechanisms that are believed to be responsible for drug resistance and the current strategies being investigated to overcome drug resistance.
Abstract: A subset of breast cancers is marked by overexpression of HER2 receptor and activated HER2-mediated signaling. Targeting HER2 offers a unique therapeutic approach for the treatment of such breast cancers. Trastuzumab, lapatinib, and, more recently, pertuzumab, have been approved by FDA to treat HER2 overexpressing breast cancers. Although the drugs effectively target HER2 leading to a favorable clinical response in patients initially, a majority of patients turn refractory to HER2 targeted drugs as early as within a year of administration. Trastuzumab, being the first HER2 targeted drug, has been investigated in detail in relation to acquired resistance, and emerging reports are evident for such drug resistance in lapatinib treated HER2 overexpressing breast cancers as well. This chapter takes a look at the progress of treatment options in HER2 overexpressing breast cancers with focus on mechanisms that are believed to be responsible for drug resistance. We also discuss the current strategies being investigated to overcome drug resistance.

6 citations


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