Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Expert perspectives on biosimilar monoclonal antibodies in breast cancer

Abstract: While biosimilars of low molecular-weight biologics such as G-CSF have been available in Europe since 2006, biosimilars of monoclonal antibodies (mAbs) have only become available in the last year. Unlike G-CSF, mAbs are large and complex and often play a direct role in the survival of patients with life-threatening illnesses such as breast cancer. Several biosimilars are currently under development for the treatment of breast cancer, and the use of biosimilars in a setting that directly impacts patient survival raises a number of questions. In this review, we discuss the biosimilar mAbs currently in development for the treatment of breast cancer. We provide an overview of the European Medicine Agency guidelines and historic data on the development of biosimilars in order to discuss the development of biosimilar mAbs for breast cancer. Biosimilars offer a highly attractive path toward reducing the cost of medical care and should be pursued with great interest. However, for agents used to treat life-threatening diseases such as cancer, a cautious approach must be taken to ensure that there is no negative impact on patient care. Clinical trials for biosimilar mAbs must be carried out in an appropriately sensitive patient population using endpoints that can accurately demonstrate both the similarity of the biosimilar and its efficacy in the indication. Due to the abbreviated approval pathway, rigorous pharmacovigilance must be in place once a biosimilar mAb is approved in order to ensure its long-term safety and efficacy.

Population pharmacokinetic and covariate analysis of pertuzumab, a HER2‑targeted monoclonal antibody, and evaluation of a fixed, non‑weight‑based dose in patients with a variety of solid tumors

Abstract: To characterize the population pharmacokinetics (PK) of pertuzumab across clinical trials in a variety of solid tumors, evaluate the potential impact of patient characteristics on PK, and confirm the appropriateness of the fixed (non-weight-based) dose Pertuzumab concentration data collected following intravenous administration during eleven phase I/II studies and the pivotal phase III trial CLEOPATRA were analyzed using nonlinear mixed-effects modeling The potential impact of patient and laboratory characteristics and HER2 target-related variables on pertuzumab PK were investigated in a covariate analysis The final model was used to confirm selection of fixed, non-weight-based dosing of pertuzumab, and to compare pertuzumab PK in CLEOPATRA with the other studies The analysis included 4,525 serum concentration measurements from 481 patients with solid tumors Pertuzumab PK in the 2–25 mg/kg dose range was described by a two-compartment linear model with first-order elimination The elimination clearance and central compartment volume were 0235 L/day, and 311 L, respectively, and the terminal elimination half-life was 180 days Baseline serum albumin and lean body weight had statistically significant effects on pertuzumab clearance; however, simulations showed that the magnitude of their effects on pertuzumab exposure was minimal compared with overall variability and was not clinically relevant Thus, variations in these factors do not require dose adjustments The fixed, non-weight-based dosing of pertuzumab, 840 mg loading dose followed by a 420 mg maintenance dose every 3 weeks, in patients with the solid tumors in this analysis is well supported by the population pharmacokinetic modeling and simulation results

Ultraearly hematoma growth in active intracerebral hemorrhage.

Abstract: Objective: To determine the association of ultraearly hematoma growth (uHG) with the CT angiography (CTA) spot sign, hematoma expansion, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: We analyzed data from 231 patients enrolled in the multicenter Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT study. uHG was defined as baseline ICH volume/onset-to-CT time (mL/h). The spot sign was used as marker of active hemorrhage. Outcome parameters included significant hematoma expansion (>33% or >6 mL, primary outcome), rate of hematoma expansion, early neurologic deterioration, 90-day mortality, and poor outcome. Results: uHG was higher in spot sign patients ( p p 4.7 mL/h ( p = 0.002) and the CTA spot sign ( p = 0.030) showed effects on rate of hematoma expansion but not its interaction (2-way analysis of variance, p = 0.477). uHG >4.7 mL/h improved the sensitivity of the spot sign in the prediction of significant hematoma expansion (73.9% vs 46.4%), early neurologic deterioration (67.6% vs 35.3%), 90-day mortality (81.6% vs 44.9%), and poor outcome (72.8% vs 29.8%), respectively. uHG was independently related to significant hematoma expansion (odds ratio 1.06, 95% confidence interval 1.03–1.10) and clinical outcomes. Conclusions: uHG is a useful predictor of hematoma expansion and poor clinical outcomes in patients with acute ICH. The combination of high uHG and the spot sign is associated with a higher rate of hematoma expansion, highlighting the need for very fast treatment in ICH patients.

Geographic and Ethnic Heterogeneity of Germline BRCA1 or BRCA2 Mutation Prevalence Among Patients With Metastatic Pancreatic Cancer Screened for Entry Into the POLO Trial

Abstract: PURPOSEGermline BRCA1 and/or BRCA2 mutations (gBRCAms) are risk factors for pancreatic cancer. The extent to which demographic and geographic factors affect the uptake of gBRCAm testing in pancreat...

The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: An exploratory, hypothesis-generating study

Abstract: Acinic cell carcinoma (ACC) of the breast is a rare form of triple-negative (that is, oestrogen receptor-negative, progesterone receptor-negative, HER2-negative) salivary gland-type tumour displaying serous acinar differentiation. Despite its triple-negative phenotype, breast ACCs are reported to have an indolent clinical behaviour. Here, we sought to define whether ACCs have a mutational repertoire distinct from that of other triple-negative breast cancers (TNBCs). DNA was extracted from microdissected formalin-fixed, paraffin-embedded sections of tumour and normal tissue from two pure and six mixed breast ACCs. Each tumour component of the mixed cases was microdissected separately. Tumour and normal samples were subjected to targeted capture massively parallel sequencing targeting all exons of 254 genes, including genes most frequently mutated in breast cancer and related to DNA repair. Selected somatic mutations were validated by targeted amplicon resequencing and Sanger sequencing. Akin to other forms of TNBC, the most frequently mutated gene found in breast ACCs was TP53 (one pure and six mixed cases). Additional somatic mutations affecting breast cancer-related genes found in ACCs included PIK3CA, MTOR, CTNNB1, BRCA1, ERBB4, ERBB3, INPP4B, and FGFR2. Copy number alteration analysis revealed complex patterns of gains and losses similar to those of common forms of TNBCs. Of the mixed cases analysed, identical somatic mutations were found in the acinic and the high-grade non-acinic components in two out of four cases analysed, providing evidence of their clonal relatedness. In conclusion, breast ACCs display the hallmark somatic genetic alterations found in high-grade forms of TNBC, including complex patterns of gene copy number alterations and recurrent TP53 mutations. Furthermore, we provide circumstantial genetic evidence to suggest that ACCs may constitute the substrate for the development of more aggressive forms of triple-negative disease.