Safety profile of subcutaneous trastuzumab in patients with HER2-positive early breast cancer: The French HERmione non-interventional prospective study.

OBJECTIVES: HERmione study was conducted to assess, in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC), the safety profile of subcutaneous (SC) formulation of trastuzumab in real-life in France. MATERIALS AND METHODS: This prospective, non-interventional study included 511 patients planned to be treated in both neoadjuvant and adjuvant settings with a follow-up of 12 months maximum in 101 sites. The safety analyses concerned 505 patients. Primary endpoint was the description of systemic safety and local tolerability of the SC trastuzumab. RESULTS: The median age of patients was 58 years. Over the study, 2449 adverse events (AEs) occurred in 422 (83.6%) patients (asthenia, arthralgia, radiation skin injury, myalgia, hot flush and diarrhea in ≥10% of patients): 92 AEs (3.8%) were grade ≥3 (radiation skin injury in 1.8% of patients and febrile neutropenia in 1.4% of patients), 76 (3.1%) were serious (mainly febrile neutropenia in 1.4% of patients) and 336 (13.7%) were treatment-related (mainly injection site pain in 9.1% of patients). Congestive Heart Failure occurred in 58 (11.5%) patients and was related to treatment in 4.6% of patients. Only 34 AEs (1.4%) in 27 (5.4%) patients led to permanent treatment discontinuation. One death was assessed as not treatment-related. Quality of life (QoL) analyses showed no deterioration of global health status. CONCLUSION: The HERmione study showed that, in a real-life setting, the safety of SC trastuzumab administered in HER2-positive eBC patients is consistent with data reported from previous clinical trials, without new safety concerns or QoL deterioration.

"Doctor, can I have less frequent injection with highly efficient treatment?" A patient centered study using an electronic choice-based conjoint analysis (ePRO) to assess real world preferences regarding erythropoiesis stimulating agent to treat anaemia in chronic kidney disease (PERCEPOLIS study).

OBJECTIVES: Patient's perception analysis appears recently in numerous studies. Conjoint analysis has been used extensively by market researchers for studying how people value the characteristics of products and services. This technique was used in a clinical study to describe perceptions and preferences of anaemic patients suffering from chronic kidney disease not on dialysis (CKDnd), regarding erythropoietin stimulating agents (ESA). METHODS: PERCEPOLIS was a French multicenter prospective non-interventional study designed to describe the relative importance of ESA attributes according to CKDnD patients. Patients fulfilled questionnaires using an electronic device (digital tablet) at baseline and after 6 months under continuous erythropoietin receptor activator (CERA) treatment. Choice-based conjoint (CBC) questionnaires were developed with multiple components: 7 ESA attributes (2 or 3 levels per attribute), 2 partial profiles per task (2 out of the 7 attributes), and 7 tasks per questionnaire. Analyses were performed according to previous ESA treatment or not. RESULTS: From 789 analyzed patients, 433 non ESA-naive patients were more than 80% to declare treatment efficacy as the most important expectative in ESA choice process (direct question) but CBC analyses revealed that frequency of injections was more crucial (relative mean weight: ∼30% versus ∼20% for efficacy). Pain at injection site and haemoglobin not exceeding the recommended target were confirmed as important criteria for patients (relative mean weights: ∼15%). No new or unexplained safety signals were noted. CONCLUSIONS: Using CBC design for the first time in a non-interventional ESA study with an electronic Patient Reported Outcome (ePRO) in an elderly population, these data showed that monthly injections and treatment efficacy were key patients' expectations relative to ESAs. CERA efficacy to maintain stable haemoglobin within the recommended range was confirmed in real-life conditions.

Endogenous Myc controls mammalian epidermal cell size, hyperproliferation, endoreplication and stem cell amplification.

The transcription factor Myc (c-Myc) plays an important role in cell growth and cell death, yet its physiological function remains unclear. Ectopic activation of Myc has been recently suggested to regulate cell mass, and Drosophila dmyc controls cellular growth and size independently of cell division. By contrast, it has been proposed that in mammals Myc controls cell division and cell number. To gain insights into this debate we have specifically knocked out Myc in epidermis. Myc epidermal knockout mice are viable and their keratinocytes continue to cycle, but they display severe skin defects. The skin is tight and fragile, tears off in areas of mechanical friction and displays impaired wound healing. Steady-state epidermis is thinner, with loss of the proliferative compartment and premature differentiation. Remarkably, keratinocyte cell size, growth and endoreplication are reduced, and stem cell amplification is compromised. The results provide new and direct evidence for a role for endogenous Myc in cellular growth that is required for hyperproliferative cycles and tissue homeostasis.

A keratin K5Cre transgenic line appropriate for tissue-specific or generalized Cre-mediated recombination.

We describe here a mouse line bearing a bovine keratin K5Cre recombinase transgene. These mice showed a dual pattern of Cre-mediated recombination, depending on the parent transmitting the transgene. In paternal transmission, recombination occurred specifically in the skin and stratified epithelia-as expected according to the expression of endogenous keratin K5. However, constitutive recombination between loxP sites transmitted by the sperm took place when the mother possessed the K5Cre transgene, even when the transgene was absent in the progeny. Cre expression in late-stage oocytes, with the Cre protein persisting into the developing embryo, leads to the constitutive recombination observed. Thus, this transgenic line allows for both tissue-specific and generalized recombination, depending on the breeding scheme.