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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: Among the new anti-HER2 agents, second-generation tyrosine kinase inhibitors and bifunctional antibodies are promising approaches that will help to improve disease control and curability of HER2-positive breast cancers.
Abstract: Purpose of review HER2-positive breast cancers have benefited since the end of the twentieth century, not only from the improvement of biological knowledge, but also from major technological advances. The latter allowed the synthesis of the first generation of enzymatic inhibitors of the HER receptor family such as lapatinib, but above all, monoclonal antibodies such as trastuzumab or pertuzumab having profoundly modified the management of these cancers. However, despite outstanding progresses, there are still patients who are not cured with these first-generation treatments, and they will need new approaches to improve disease control and impact patients' survival. Recent findings Understanding the mechanisms of escape to these treatments, more than real resistance, has profoundly changed our pharmacological approaches. They have enabled the development of molecules blocking the signaling pathway downstream of receptors such as mTOR, PI3K inhibitors or molecules interacting with the cellular traffic of the receptor in combination with the first-generation treatments. In addition, new second-generation tyrosine kinase inhibitors have demonstrated increased in-vitro efficacy, but still need to show clinical relevance because of new toxicity profiles. The antibody engineering had also permitted a paradigm evolution of the role of the antibody treatments, particularly with the synthesis of bispecific and trifunctional antibodies, promoting the link between the tumor and the immune system, with the goal to amplify the immune anticancer response. Summary Among the new anti-HER2 agents, second-generation tyrosine kinase inhibitors and bifunctional antibodies are promising approaches that will help to improve disease control and curability of HER2-positive breast cancers.

9 citations

Journal ArticleDOI
TL;DR: Pertuzumab with trastuzumsumab plus docetaxel was effective in reducing the brain metastases from breast cancer.
Abstract: The CLEOPATRA trial reported the survival benefit of pertuzumab with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer patients. However, there are a few case reports concerning the effects of a pertuzumab-containing regimen on brain metastases. A 55-year-old woman, who underwent curative surgery for breast cancer after neoadjuvant chemotherapy 5 years previously, developed repeated solitary brain metastasis in her right occipital lobe. Whole brain radiation therapy, stereotactic radiosurgery and 3 times of surgical resection were performed. Lapatinib and capecitabine plus tamoxifen were administered. The metastasis recurred in the stump of the previous surgery. Pertuzumab with trastuzumab plus docetaxel was initiated as second-line chemotherapy. A complete response of the brain metastasis was achieved, which persisted for 5 months. Pertuzumab with trastuzumab plus docetaxel was effective in reducing the brain metastases from breast cancer. Further studies are warranted to confirm the effect of this regimen on brain metastases.

9 citations

Journal ArticleDOI
TL;DR: In this article , a single-arm prospective trial, patients with treatment-naïve stage II-III HER2+ breast cancer received neoadjuvant weekly paclitaxel ×12 and pertuzumab ×4 every 3 weeks ×4.
Abstract: De-escalating adjuvant therapy following pathologic complete response (pCR) to an abbreviated neoadjuvant regimen in human epidermal growth factor receptor 2-positive (HER2+) breast cancer is the focus of international research efforts. However, the feasibility of this approach and its appeal to patients and providers had not been formally investigated. We aimed to assess adherence to de-escalated adjuvant antibody doublet therapy (trastuzumab and pertuzumab [HP], without chemotherapy) among patients with pCR following neoadjuvant paclitaxel/HP (THP). In this single-arm prospective trial, patients with treatment-naïve stage II-III HER2+ breast cancer received neoadjuvant weekly paclitaxel ×12 and HP every 3 weeks ×4. The primary endpoint was receipt of adjuvant non-HER2-directed cytotoxic chemotherapy. Ninety-eight patients received ≥1 dose of THP on study. Patients had median age of 50 years, 86% had stage II tumors, and 34% were hormone receptor-negative. Five patients had incomplete clinical response following THP and received doxorubicin and cyclophosphamide before surgery; they were classified as non-pCR and censored from further analyses. The overall pCR rate was 56.7%. Among patients with pCR, the adherence rate to de-escalated antibody-only therapy (HP) was 98.2% (95% CI 90.3-100.0%), and the primary feasibility endpoint was reached. The majority of patients felt positive or neutral about their adjuvant treatment plans. With brief follow-up (median 19.1 months), there were no breast cancer recurrences. De-escalation of adjuvant chemotherapy among patients who experience pCR in early-stage HER2+ breast cancer is a practicable approach for both patients and physicians. Planned and ongoing prospective trials will determine the long-term efficacy of this approach.Trial registration clinicaltrials.gov, NCT03716180, https://clinicaltrials.gov/ct2/show/NCT03716180 .

9 citations

Proceedings ArticleDOI
TL;DR: The GeparSepto trial will investigate the efficacy of neoadjuvant nab-paclitaxel compared to solvent based pac litaxel given weekly and the dual blockade with Trastuzumab and PertuzumAB in HER 2 positive BC.
Abstract: Background: Anthracycline/taxane based regimen are standard of care for neoadjuvant therapy in breast cancer. Recent data from the neo-Tango study suggest that a reverse sequence of taxane followed by the anthracycline can achieve higher pCR rates. Solvent-based taxanes (paclitaxel, docetaxel) cause severe toxicities most likely by the solvents such as cremophor. Nab-paclitaxel is a solvent-free formulation of paclitaxel encapsulated in albumin. It is believed that nab-Paclitaxel compared to solvent based paclitaxel followed by conventional dosed EC might further improve the pCR rate in breast cancer patients receiving neoadjuvant treatment. Previous studies have shown that dual anti-HER blockade is superior to trastuzumab alone resulting in an increase of pCR rate by 20%. Patients and Methods: The GeparSepto trial, a neoadjuvant, randomized phase III study, planned to include 1200 pts, randomized to nab-paclitaxel versus conventional, solvent based paclitaxel given weekly for 12 weeks followed in both arms by 4 cylces conventionally dosed EC. The primary objective is to compare the rate of pCR (ypT0 + ypN0). Further objectives are to compare the pCR rate in predefined subgroups, pCR by other definition, the clinical response rate and the rate of breast conserving surgery after chemotherapy in the two different treatment arms. Women with untreated, histologically confirmed uni- or bilateral, cT2- cT4d carcinoma, and no clinically relevant cardiovascular and other co-morbidities are randomized to receive either paclitaxel (80mg/m2) or nab-paclitaxel (150 mg/ m2) day 1, 8, 15, q d 22 for 4 cycles followed by conventional EC (E (90mg/m2)+C (600 mg/m2)) on day 1 q day 22 for 4 cycles. HER2 positive pts receive trastuzumab (loading dose 8mg/kg followed by 6 mg/kg) and pertuzumab (loading dose 840 mg followed by 420 mg) q3w concomitantly to the chemotherapy. Biomaterial including FFPE form core biopsy, serum, plasma, full blood is collected before randomization, after the 12 cycles for (nab−) paclitaxel therapy and after the 4 cycles of EC before surgery. The HER2, estrogen receptor, progesterone receptor, Ki67 and SPARC status will be centrally tested by immunohistochemistry prior to randomization for stratification. A broad translational program is planned. It has been assumed that solvent based taxane will achieve an overall pCR rate of 33% to be increased using nab-paclitaxel to 41%, corresponding to an odds ratio of 1.41. If 596 patients are enrolled into each arm, a χ2-test will have an 80% power with a 2-sided significance level α=0.05 to show the superiority of nab-paclitaxel. Closed test procedure will be used to test for non-inferiority of nab-paclitaxel first. The trial is registered under NCT01583426. It is financially supported by Roche and Celgene. Results: The centres have been initiated after approval by ethics committee and authorities. First patient in will be this months. It is planned to recruit 18 months in 100 sites in Germany. Conclusion: Geparsepto will investigate the efficacy of neoadjuvant nab-paclitaxel compared to solvent based paclitaxel given weekly and the dual blockade with Trastuzumab and Pertuzumab in HER 2 positive BC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-11.

9 citations

Journal ArticleDOI
TL;DR: This simulation model suggests that substantial progress has been made in treating HER2+ women over the past 15 years, and the future may witness similar gains with the introduction of pertuzumab.

9 citations


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