Topic
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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TL;DR: In this article , the authors developed a new antibody-drug conjugate, trastuzumab emtansine, which is a potent cytotoxic agent bound to trastusumab and is currently a standard therapeutic strategy for HER2-positive metastatic breast cancer.
Abstract: HER2-positive breast cancer is an aggressive disease. As a result of the development of specific HER2-targeted therapies, such as trastuzumab, more than 20 years ago, the prognosis of these patients has improved. Metastatic HER2-positive breast cancer patients are achieving better survival rates upon treatment with anti-HER2 therapies than patients with HER2-negative disease. Double HER2 blockade with trastuzumab and pertuzumab combined with a taxane achieved an unprecedented survival of over 57 months in first-line patients. Trastuzumab emtansine, the first antibody-drug conjugate approved for patients in second-line treatment was a potent cytotoxic agent bound to trastuzumab and is currently a standard therapeutic strategy. Despite the progress in treatment development, most patients develop resistance and eventually relapse. Advances in the design of antibody-drug conjugates have led to the development of new generation drugs with enhanced properties, such as trastuzumab deruxtecan and trastuzumab duocarmazine, which are significantly changing the paradigm in the treatment of HER2-positive metastatic breast cancer.
2 citations
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TL;DR: Interest has been focused on the impact of trastuzumab, a human epidermal growth factor receptor-2 (HER2) blocker, on left ventricular (LV) function.
Abstract: Whereas breast cancer therapy may target cardiovascular system through side effects of surgery, chemotherapy, and radiation, interest has been focused on the impact of trastuzumab [(1)][1], a human epidermal growth factor receptor-2 (HER2) blocker, on left ventricular (LV) function. Maximizing HER2
2 citations
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TL;DR: Prior exposure to pertuzumab did not impact survival outcomes in patients receiving T-DM1 for metastatic HER2-positive breast cancer, with none of these measures being statistically different than those estimated for the pertuzumsumab-naïve group.
Abstract: Docetaxel in combination with two HER2-directed therapies, trastuzumab and pertuzumab, is the current standard frontline therapy for patients with metastatic HER2-positive breast cancer Ado-trastuzumab (T-DM1), an antibody-drug conjugate of trastuzumab and a cytotoxic microtubule-inhibitory agent, emtansine, is approved in patients that have progressed with prior trastuzumab-based therapy However, the benefit of T-DM1 in patients previously treated with pertuzumab therapy for metastatic breast cancer remains unclear We identified thirty-three adults with metastatic HER2-positive breast cancer treated between March 2013 and July 2018 with T-DM1 either as subsequent therapy after progression on a pertuzumab-based regimen (ie, “pertuzumab-pretreated”) or without prior exposure to pertuzumab (ie, “pertuzumab-naive”) Collected data included patient demographics, treatment history, adverse events, and clinical outcomes For both cohorts receiving T-DM1, the primary endpoint was PFS and secondary endpoints were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and T-DM1-related toxicity rate Pertuzumab-pretreated patients (n = 23, with 21 evaluable for T-DM1 efficacy) had a median PFS of 95 months (95% CI: 29–NA), 1-year OS rate of 674% (95% CI: 500–909%) with an unreached median, ORR of 143% (95% CI: 30–363%), and CBR of 524% (95% CI: 298–743%), with none of these measures being statistically different than those estimated for the pertuzumab-naive group (n = 10) Treatment with T-DM1 after prior pertuzumab exposure (median T-DM1 duration 29 months) resulted in no grade ≥ 3 adverse events In our cohort, prior exposure to pertuzumab did not significantly impact T-DM1’s clinical efficacy or safety profile as second- or later-line therapy in patients with metastatic HER2-positive breast cancer
2 citations
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TL;DR: In this article , the real-world efficacy and toxicity of neoadjuvant trastuzumab and pertuzumaab combined with chemotherapy for HER2-positive breast cancers (BC) have been investigated.
Abstract: Background Randomized studies of neoadjuvant (NA) trastuzumab and pertuzumab combined with chemotherapy for HER2-positive breast cancers (BC) have reported pathological complete response (pCR) rates of 39 to 61%. This study aimed to determine the real-world efficacy and toxicity of NA trastuzumab and pertuzumab combined with chemotherapy in a UK tertiary referral cancer centre. Methods HER2-positive early BC patients given neoadjuvant chemotherapy with trastuzumab and pertuzumab between October 2016 and February 2018 at our tertiary referral cancer centre were identified via pharmacy records. Clinico-pathological information, treatment regimens, treatment-emergent toxicities, operative details, and pathological responses and outcomes were recorded. Results 78 female patients were identified; 2 had bilateral diseases and 48 of 78 (62%) were node positive at presentation. 55 of 80 (71%) tumours were ER-positive. PCR occurred in 37 of 78 (46.3%; 95% CI: 35.3–57.2%) patients. 14 of 23 (60.8%) patients with ER-negative tumours achieved pCR; 23 of 55 (41.8%) were ER-positive and 6 of 19 (31.6%) were ER-positive and PgR-positive. No cardiac toxicity was documented. Diarrhoea occurred in 53 of 72 (74%) patients. Grade 3–4 toxicity occurred in ≥2% patients. These were diarrhoea, fatigue, and infection. The Median follow up period was 45.2 months (95% CI 43.8–46.3) with 71 of 78 (91.0%) remaining disease-free and 72 of 78 (92.3%) alive. Estimated OS at 2 years 86% (95% CI: 75–99%). Conclusion This data confirms the efficacy of neoadjuvant chemotherapy combined with dual HER2 directed therapy. While no cardiac toxicity was observed, diarrhoea occurred frequently. The low pCR rate observed in ER and PgR-positive BCs warrants further investigation and consideration of strategies to increase the pCR rate.
2 citations
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18 Mar 2015
TL;DR: In this article, a bispecific antibody for targeting different epi-positions of the ErbB2 molecule is constructed by utilizing a bioengineering technology, and an expression vector which is used for coding the DNA sequence of the antibody and contains the DNA sequences, and a host cell containing the expression vector.
Abstract: The invention belongs to the biotechnical field and provides a bispecific antibody for treating breast cancer. An antigen binding region of the anti-ErbB2 bispecific antibody for treating breast cancer consists of a Trastuzumab antibody and a Pertuzumab antibody. A bispecific antibody for targeting different epi-positions of the ErbB2 molecule is constructed by utilizing a bioengineering technology. The invention further provides an expression vector which is used for coding the DNA sequence of the antibody and contains the DNA sequence, and a host cell containing the expression vector. The bispecific antibody for treating breast cancer provided by the invention can be specially combined with a region II and a region IV outside an ErbB2 molecule cell, and has remarkable effects of resisting against the breast cancer in vitro and in vivo.
2 citations