Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Assessment of factors associated with community-onset Extended Spectrum Beta-Lactamase producing Escherichia coli urinary tract infections in France

Importance. Extended Spectrum Beta-Lactamase producing Escherichia coli is considered as a leading pathogen contributing to the global burden of antimicrobial resistance. Objective. The objective of this study was to better understand factors associated with the heterogeneity of community-onset ESBL-E. coli urinary tract infections (UTI) across France. Design. Cross-sectional study. Setting. 59 administrative departments of metropolitan France. Participants. This cross-sectional study performed in 2021 was based on data collected by the French nationwide network of clinical laboratories (PRIMO). E. coli strains isolated from community urine samples from January 1 to December 31 2019 for 59 administrative departments of metropolitan France were included. Main measure. Using quasi-Poisson regression models, we assessed the associations between several ecological factors available on government and administration websites for years 2010 to 2020 (demographic population structure, living conditions, baseline health-care services, antibiotic consumptions, economic indicators, animal farming density and environmental characteristics) and the number of ESBL producing strains among E.coli isolated from urine samples of individuals with community-acquired UTI in 2019. Results. Among 444,281 E. coli isolates from urine samples tested in 1,013 laboratories, the mean ESBL-E. coli prevalence was 3%. In an adjusted model, the number of community onset ESBL-E. coli UTI in each department was significantly (p <0.05) and positively associated with the percentage of children <5 year-old, overcrowded households, consumption of fluoroquinolones and tetracyclines (DDJ / 1000 inhabitants), and the poultry density. The social disadvantage index and the proportion of water surface were negatively associated with a higher number of community-onset ESBL-E. coli UTI. Conclusions. In this cross-sectional study, we confirmed the impact of fluoroquinolone usage and poultry density on the epidemiology of community-onset ESBL-E. coli UTI. Strategies to mitigate ESBL in the community should address the role played by tetracycline, overcrowded households and preschool children