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: A case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma, which demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate.
Abstract: Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.
13 citations
TL;DR: A peptide (58F63Y) with the lowest binding free energy was confirmed experimentally to have the highest affinity and may be used as a new probe in diagnosing and treating HER2-positive breast cancer.
Abstract: A high level of HER2 expression in breast cancer correlates with a higher tumor growth rate, high metastatic potential, and a poor long-term patient survival rate. Pertuzumab, a human monoclonal antibody, can reduce the effect of HER2 overexpression by preventing HER2 dimerization. In this study, a combination protocol of molecular dynamics modeling and MM/GBSA binding free energy calculations was applied to design peptides that interact with HER2 based on the HER2/pertuzumab crystal structure. Based on a β hairpin in pertuzumab from Glu46 to Lys65-which plays a key role in interacting with HER2-mutations were carried out in silico to improve the binding free energy of the hairpin that interacts with the Phe256-Lys314 of the HER2 protein. Combined the use of one-bead-one-compound library screening, among all the mutations, a peptide (58F63Y) with the lowest binding free energy was confirmed experimentally to have the highest affinity, and it may be used as a new probe in diagnosing and treating HER2-positive breast cancer.
13 citations
TL;DR: Clinical trials demonstrate improved outcomes, with minimal increases in toxicity with the addition of pertuzumab to trastuzumAB in patients with HER2-positive metastatic breast cancer, indicating the advantage of dual HER2 receptor blockade.
Abstract: Pertuzumab is a humanized monoclonal antibody directed at the dimerization domain of the receptor tyrosine-protein kinase erbB-2 (HER2) receptor. It possesses a unique and complimentary mechanism of action compared to trastuzumab, which has historically been the cornerstone of therapy for HER2-amplified breast cancer. Clinical trials demonstrate improved outcomes, with minimal increases in toxicity with the addition of pertuzumab to trastuzumab in patients with HER2-positive metastatic breast cancer, indicating the advantage of dual HER2 receptor blockade. Pertuzumab is approved as first-line therapy in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer, with future opportunities to investigate its efficacy in other stages of breast cancer, as well as in the treatment of other malignancies.
12 citations
TL;DR: Bvacizumab, pertuzumab and octreotide depot was well-tolerated with a 16% ORR and results in the well-differentiated carcinoid tumors are thought provoking.
Abstract: Purpose: To evaluate efficacy and safety of bevacizumab, pertuzumab, and octreotide depot for advanced neuroendocrine tumors.Methods: Patients received bevacizumab 15 mg/kg and pertuzumab 420 mg IV q21 days with octreotide depot 30 mg IM q28 days.Results: Toxicities in 43 patients included diarrhea (63%), fatigue (63%), hypertension (44%), and nausea (44%). Reversible G3 hypertension (26%) and LVEF decline (9%) occurred. 7/43 patients achieved objective response (typical carcinoid, 5; pancreatic NET, 2). Median PFS and OS were 6.5 and 26.4 months, respectively.Discussion: Bevacizumab, pertuzumab, and octreotide depot was well-tolerated with a 16% ORR. Results in the well-differentiated carcinoid tumors are thought provoking.
12 citations
TL;DR: HF incidence during trastuzumab/pertuzumAB or TDM1 therapy in this real-world cohort was low, and survival in this cohort was worse compared to RCT, suggesting that recruitment of patients similar to the real- world population is required.
Abstract: Little data exist for comparing cardiac safety and survival outcomes of trastuzumab/pertuzumab or ado-T emtansine (TDM1) in metastatic breast cancer (MBC) patients enrolled in randomized clinical trial (RCT) vs the real-world. This was a retrospective population-based cohort of all patients with MBC treated with trastuzumab/pertuzumab or TDM1 (2012–2017) in Ontario, Canada. Outcomes were incident heart failure (HF) and overall survival (OS). RCT data were obtained from digitizing survival curves and compared with cohort data using Kaplan–Meier analysis. Age-based comparison of outcomes was conducted for patients ≥ 65 years old vs younger than 65. The two cohorts composed of 833 and 397 patients treated with trastuzumab/pertuzumab and TDM1, of whom 5.5% and 7.6% had baseline HF, respectively. Incident HF following trastuzumab/pertuzumab or TDM1 was low (trastuzumab/pertuzumab 1.8 events/100 person years; TDM1 0.02 events/100 person years). The median OS was 39.2 and 56.4 months in the trastuzumab/pertuzumab population-based cohort and CLEOPATRA, respectively. The median OS was 15.4 and 30.9 months in the TDM1 population-based cohort and EMILIA, respectively. Cohort OS was significantly worse than RCT OS (trastuzumab/pertuzumab HR 1.67, 95% CI 1.37–2.03, p < 0.0001; TDM1 HR 2.80, 95% CI 2.27–3.44, p < 0.0001). Older patients had worse OS than younger patients for trastuzumab/pertuzumab (HR 1.60, 95% CI 1.19–2.16, p = 0.0018), but not for TDM1 (HR 1.16, 95% CI 0.81–1.66, p = 0.43). HF incidence during trastuzumab/pertuzumab or TDM1 therapy in this real-world cohort was low. Survival in this cohort was worse compared to RCT, suggesting that recruitment of patients similar to the real-world population is required.
12 citations