PURPOSETrastuzumab deruxtecan (T-DXd, formerly DS-8201a) is a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload. ...

Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study.

The major current conventional types of metastatic breast cancer (MBC) treatments include surgery, radiation, hormonal therapy, chemotherapy, or immunotherapy. Introducing biological drugs, targeted treatment and gene therapy can potentially reduce the mortality and improve the quality of life in patients with MBC. However, combination of several types of treatment is usually recommended. Triple negative breast cancer (TNBC) accounts for 10–20% of all cases of breast carcinoma and is characterized by the low expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2). Consequently, convenient treatments used for MBC that target these receptors are not effective for TNBC which therefore requires special treatment approaches. This review discusses the occurrence of MBC, the prognosis and predictive biomarkers of MBC, and focuses on the novel advanced tactics for treatment of MBC and TNBC. Nanotechnology-based combinatorial approach for the suppression of EGFR by siRNA and gifitinib is described.

/pdf/metastatic-and-triple-negative-breast-cancer-challenges-and-1tdrraq0p1.pdf

Metastatic and triple-negative breast cancer: challenges and treatment options.

Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. The article covers different indications, treatment settings, administration volumes, and injection devices. We focus on biotherapeutics in rheumatoid arthritis (RA), immunoglobulin-replacement therapy in primary immunodeficiency (PI), beta interferons in multiple sclerosis (MS), and monoclonal antibodies (mAbs) in oncology. While most subcutaneous biotherapeutics in RA, PI, and MS are self-administered at home, mAbs for oncology are still only approved for administration in a healthcare setting. Beside concerns around the safety of biotherapeutics in oncology, a key challenge for self-administration in this area is that doses and dosing volumes can be comparatively large; however, this difficulty has recently been overcome to some extent by the development of high-concentration solutions, the use of infusion pumps, and the coadministration of the dispersion enhancer hyaluronidase. Furthermore, given the increasing number of biotherapeutics being considered for combination therapy and the high dosing complexity associated with these, especially when administered intravenously, subcutaneous delivery of fixed-dose combinations might be an alternative that will diminish these burdens on healthcare systems.

/pdf/subcutaneous-administration-of-biotherapeutics-an-overview-2i3wag363f.pdf

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities

In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra- and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. By integration with single cell data, we spatially map tumor-associated cell types to find tertiary lymphoid-like structures, and a type I interferon response overlapping with regions of T-cell and macrophage subset colocalization. We construct a predictive model to infer presence of tertiary lymphoid-like structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define a high resolution map of cellular interactions in tumors and provide tools generalizing across tissues and diseases.

/pdf/spatial-deconvolution-of-her2-positive-breast-cancer-9hyxard7qd.pdf

Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions

Background: We aimed to determine the distribution of intrinsic subtypes within HER2-low breast cancer (BC), and to describe the prognostic impact of HER2-low status on survival outcomes. Methods: This is a retrospective, observational study of primary BC extracted from The Cancer Genome Atlas dataset. We described the distribution of PAM50 intrinsic subtypes within HER2-low BC subtype according to hormonal receptor status (positive (HR+) and negative (HR−)). Secondly, we assessed the impact of HER2-low on survival outcomes (progression-free interval (PFI), disease-free interval (DFI), and overall survival (OS)). Results: We analyzed 804 primary BCs, including 410 (51%) HER2-low BCs (336 HR+ and 74 HR−). The proportion of HER2-enriched tumors was higher in the HER2-low/HR− group compared to HER2-low/HR+ (13.7% versus 1.2%, respectively). HER2-enriched tumors were more frequent in HER2-low/HR− and HER2-low/HR+ subtypes, compared to HER2-negative/HR− and HER2-negative/HR+ subtypes, respectively (13.7% versus 1.6% and 1.2% versus 0.5%, respectively). We observed no significant differences in PFI, DFI, and OS between HER2-low subtypes and each non-HER2-low subtype paired by HR status. Conclusions: Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer may explain the different clinical behaviors and responses to treatment, and ultimately support further investigation of new treatment strategies in the HER2-low category. Moreover, it highlights the importance of considering HR status in the HER2-low category.

https://www.mdpi.com/2072-6694/13/11/2824/pdf

HER2-Low Breast Cancer: Molecular Characteristics and Prognosis.

Despite the important advances observed in the last 25 years in the comprehension of the clinical and biological nature of breast cancer and its treatment, this disease remains a significant cause of cancer morbidity and mortality worldwide. The clinical trial Hera has demonstrated the safety and efficacy of trastuzumab in the treatment of HER2 positive (HER2+) breast cancer patients, in early stages, subsequent to surgery, chemotherapy (neoadjuvante or adjuvant) and radiotherapy, if applied.To evaluate the cost-effectiveness of 1-year trastuzumab treatment versus standard care (observation following standard adjuvant chemotherapy), in patients with HER2+ breast cancer in early stages from the societal and the Portuguese National Health Service (NHS) perspectives.A 5-state Markov model with annual transition cycles was developed to estimate the long term health and economic outcomes of HER2+ early breast cancer patients based on HERA clinical trial results. Portuguese NHS resource use and costs were estimated from a consensus expert panel and published unit costs, respectively. Clinical and economic outcomes were discounted at 3% per annum. The incremental cost-effectiveness ratios per life year gained (LYG) and per quality adjusted life year (QALY) gained were estimated. One-way sensitivity analysis was performed.Considering a 45 year time horizon, treatment with trastuzumab was estimated to increase discounted life expectancy by 2,114 life years and quality-adjusted life expectancy by 2,009 QALYs compared to standard care. Direct and indirect costs were projected to be 61.839 euro and 19.759 euro with trastuzumab and 40.559 euro and 25.392 euro with standard of care. These results corresponded to incremental cost-effectiveness ratios of 10.067 euro and 10.595 euro assuming direct costs only, and of 7.400 euro and 7.789 euro including indirect costs, per life year gained and per QALY gained, respectively.The 1-year trastuzumab use as adjuvant therapy in HER-2+ early breast cancer patients improves survival and can be considered a cost effective therapy with a high degree of certainty in the Portuguese setting.

/pdf/cost-effectiveness-of-trastuzumab-in-the-treatment-of-early-3oa8y5fk7a.pdf

[Cost-effectiveness of trastuzumab in the treatment of early stages breast cancer patients, in Portugal]

PERFIL DA DOENÇA ONCOLÓGICA EM PORTUGAL Racional, Objectivos e Metodologia - Estudo Perfil

The Benefit of Her-2 Targeted Therapies on Overall Survival of Patients With Metastatic Breast Cancer – A Systematic Review

ESTUDO DE AVALIAÇÃO DO CUSTO INCREMENTAL Da Auto-Monitorização de INR versus Controlo Laboratorial ou Monitorização no Centro de Saúde, em Portugal

Hospital Resources Consumption Associated with Trastuzumab Treatment in Breast Cancer in Portugal

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