Matching-Adjusted Indirect Comparison (MAIC) of Tepotinib with Other MET Inhibitors for the Treatment of Advanced NSCLC with MET Exon 14 Skipping Mutations

Introduction MET exon 14 skipping in patients with advanced non-small cell lung cancer (aNSCLC), can be targeted with MET inhibitors including tepotinib, capmatinib, savolitinib, and crizotinib. Matching-adjusted indirect comparison (MAIC) methodology was used to compare outcomes data between agents and to address bias from differences in baseline characteristics. Methods Patient-level data from the VISION study (tepotinib) were weighted for comparison with aggregate data from the GEOMETRY mono-1 (capmatinib), NCT02897479 (savolitinib) and PROFILE 1001 (crizotinib) studies in patients with aNSCLC, using baseline characteristics prognostic for overall survival (OS) in VISION. Overall response rate (ORR), OS, progression-free survival (PFS), and duration of response (DOR) were compared. Patients were stratified by line of therapy: overall (all lines), previously treated, and treatment-naive. Results Improvements in ORR and all time-to-event endpoints were predicted for tepotinib compared with crizotinib and savolitinib in the different populations, although comparisons with savolitinib were hindered by considerable differences in baseline patient populations. Tepotinib appeared to be associated with prolonged PFS and OS compared with capmatinib in previously treated patients (PFS HR 0.54; 95% CI 0.36-0.83; OS HR 0.66; 95% CI 0.42-1.06) and the overall populations (PFS HR 0.60; 95% CI 0.43-0.86; OS HR 0.72; 95% CI 0.49-1.05), with smaller improvements in DOR. The ORR comparisons between tepotinib and capmatinib identified a swing of up to +/- 6 percentage points in the weighted tepotinib ORR depending on the population studied (treatment-naive vs. previously treated patients). Conclusions The MAIC identified potential differences in efficacy endpoints with the different MET inhibitors, and predicted prolonged PFS and OS with tepotinib compared with capmatinib and crizotinib. Although MAIC cannot balance for unobserved factors, it remains an informative method to contextualize single-arm studies, where head-to-head trials are unlikely to be feasible

Health Utility Analysis of Tepotinib in Patients with Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping

OBJECTIVES: The VISION trial showed durable activity of tepotinib in MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC). We analyzed health state utilities using patient-reported outcomes from VISION. METHODS: EQ-5D-5L and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 responses were collected at baseline, every 6-12 weeks during treatment, and at end-of-treatment and safety follow-up. EQ-5D-5L and EORTC Quality of Life Utility Measure-Core 10 Dimensions (QLU-C10D) utilities were derived using US, Canada, UK and Taiwan value sets, where available. Utilities were analyzed with linear mixed models including covariates for progression or time-to-death (TTD). RESULTS: Utilities were derived for 273/291 patients (EQ-5D-5L, 1545 observations; QLU-C10D, 1546 observations). Mean (± standard deviation) US EQ-5D-5L utilities increased after tepotinib initiation, from 0.687 ± 0.287 at baseline to 0.754 ± 0.250 before independently assessed progression, and decreased post-progression (0.704 ± 0.288). US QLU-C10D utilities showed similar trends (0.705 ± 0.215, 0.753 ± 0.195, and 0.708 ± 0.209, respectively). Progression-based models demonstrated a statistically significant impact of progression on utilities and predicted higher utilities pre- versus post-progression. TTD-based models showed statistically significant associations of TTD with utilities and predicted declining utilities as TTD decreased. Prior treatment (yes/no) did not significantly predict utilities in progression- or TTD-based models. Utilities for Canada, UK and Taiwan showed comparable trends. CONCLUSIONS: In this first analysis of health state utilities in patients with METex14 skipping NSCLC, who received tepotinib, utilities were significantly associated with progression and TTD, but not prior treatment

Protocol for a systematic literature review and network meta-analysis of the clinical benefit of inhaled maintenance therapies in chronic obstructive pulmonary disease

© Author(s) (or their employer(s)) 2019. Introduction Chronic obstructive pulmonary disease (COPD) exacerbations progress the course of disease and impair lung function. Inhaled maintenance therapy reduces exacerbations. It is not yet established which inhaled therapy combination is best to reduce exacerbations, lung function decline and symptom burden. Methods and analysis MEDLINE, EMBASE and the Cochrane Library will be searched for articles between January 2011 and May 2018 using a pre-specified search strategy. Conference proceedings will be searched. Systematic reviews (with or without meta-analysis), randomised controlled trials (RCTs), cohort studies and case controlled studies comparing six interventions comprising different combinations of long-acting bronchodilators and inhaled corticosteroids in unison or on their own. The primary outcome is the reduction in moderate-to-severe exacerbations. Secondary outcomes include: lung function, quality of life, mortality and other adverse events. Titles and abstracts will screened by the primary researcher. A second reviewer will repeat this on a proportion of records. The Population, Intervention, Comparator, Outcomes and Study framework will be used for data extraction. A network meta-analyses of outcomes from RCTs and real-world evidence will be integrated if feasible. The 95% credible interval will be used to assess the statistical significance of each summary effect. Ranking of interventions will be based on their surface under cumulative ranking area. Ethics and dissemination COPD exacerbations are burdensome to patients. We aim to report results that provide clinicians with a more informed choice of which inhaled therapy combinations are best to reduce exacerbations, improve disease burden and reduce lung function and exercise capacity decline, compared with the potential harms, in certain populations with COPD. PROSPERO registration number CRD42018088013Boehringer Ingelheim Ltd. Bracknell, U

Automatic detection of crop rows in maize fields with high weeds pressure

This paper proposes a new method, oriented to crop row detection in images from maize fields with high weed pressure. The vision system is designed to be installed onboard a mobile agricultural vehicle, i.e. submitted to gyros, vibrations and undesired movements. The images are captured under image perspective, being affected by the above undesired effects. The image processing consists of three main processes: image segmentation, double thresholding, based on the Otsu’s method, and crop row detection. Image segmentation is based on the application of a vegetation index, the double thresholding achieves the separation between weeds and crops and the crop row detection applies least squares linear regression for line adjustment. Crop and weed separation becomes effective and the crop row detection can be favorably compared against the classical approach based on the Hough transform. Both gain effectiveness and accuracy thanks to the double thresholding that makes the main finding of the paper

Le diabète, un marché en pleine mutation

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Site-specific herbicide spraying can control weeds as well as full spraying in the long-term. A simulation study

International audienceSite-specific herbicide spraying reduces herbicide use as it sprays only where weeds are detected. We studied the long-term impact of this weed-control measure on weed-impact indicators (crop yield loss, biodiversity, …). We developed a submodel to simulate the effects of site-specific spraying on weed floras and included this into the existing FlorSys model. The latter simulates multiannual multispecies weed dynamics and crop canopies at a daily time-step from cropping system, weather and soil. Global sensitivity and uncertainty analyses, based on 30-year-long simulations of different rotations and weather series, identified the most influential inputs and the most sensitive outputs. The cropping system (rotation with associated sowing patterns, herbicide products and treatment dates) was more influential than the spraying system (geometrical spraying pattern, weed detection). Finally, a real-life case study was simulated to demonstrate the feasibility of reconciling crop production with reduced herbicide use, thanks to site-specific spraying

Conception de systèmes de cultures par algorithmes d’optimisation

National audienceLa construction d’un système de cultures n’est pas toujours aisée, notamment lorsque l’on souhaite prendre en compte des critères antagonistes (améliorer le rendement tout en préservant la biodiversité). Dans ce travail, nous proposons une méthode de construction de systèmes de cultures, via des algorithmes d’optimisation, en utilisant le modèle FLORSYS. Les simulations sont effectuées sur une période de 30 ans, pour 10 répétitions climatiques. Les systèmes de cultures sont construits pour maximiser/minimiser certains indicateurs de sortie. Les optimisations sont réalisées à l’aide de deux méthodes différentes, en fonction du nombre de campagnes culturales considérées : une approche par PLS-PM est conduite lorsque le choix de cultures et d’itinéraires techniques est restreint ; sinon, une approche par heuristique est utilisée. La présentation sera l’occasion de montrer des exemples d’application de cette méthode de construction et de discuter de son intérêt

Site-Specific Herbicide Spraying Can Control Weeds as Well as Full Spraying in the Long-Term. A Simulation Study

Site-specific herbicide spraying reduces herbicide use as it sprays only where weeds are detected. We studied the long-term impact of this weed-control measure on weed-impact indicators (crop yield loss, biodiversity, …). We developed a submodel to simulate the effects of site-specific spraying on weed floras and included this into the existing FlorSys model. The latter simulates multiannual multispecies weed dynamics and crop canopies at a daily time-step from cropping system, weather and soil. Global sensitivity and uncertainty analyses, based on 30-year-long simulations of different rotations and weather series, identified the most influential inputs and the most sensitive outputs. The cropping system (rotation with associated sowing patterns, herbicide products and treatment dates) was more influential than the spraying system (geometrical spraying pattern, weed detection). Finally, a real-life case study was simulated to demonstrate the feasibility of reconciling crop production with reduced herbicide use, thanks to site-specific spraying

Des technologiques innovantes pour optimiser le désherbage de précision

The reduction of herbicide use intensity can benefit from the patchy distribution of weeds in fields byshifting from whole-field to precision spraying. Herbicides are then only applied where weeds are present.To do this, we need to detect and map weeds in fields. The resulting weed presence information is thenused to direct a spraying system in order to apply herbicides only where needed.This paper first presents the weed-detection methods used in the ANR CoSAC project (aiming to designsustainable weed management strategies in a changing context) and then two precision-sprayingsystems: 1) an autonomous system based on a commercial solution (the WeedSeeker system by Trimble)which detects weeds and sprays the herbicide in a single passage, 2) a system based on establishing aweed-presence map which is used a posteriori to control the opening and closure of nozzles on thesprayer booms. For this second method, only the weed mapping part will be presented.Finally, the long-term sustainability and efficiency of precision spraying was evaluated with simulationswith the virtual-field models which predicts multiannual weed dynamics and crop production at a daily timestep from cropping-system inputs and weather data.Dans un objectif de réduction de l'intensité d'usage des herbicides, la variabilité intra-parcellaire desadventices peut être prise en compte pour effectuer un désherbage de précision : la pulvérisation n’esteffectuée qu’aux endroits où les adventices sont présentes. Avant d'effectuer cette pulvérisation localisée,il faut être en mesure de détecter, voire cartographier, les adventices. L’information de présenced’adventices est utilisée pour commander un système de pulvérisation afin d’apporter l’herbicideseulement aux endroits où cela est nécessaire.Dans cet article, après une présentation de méthodes de détection des adventices utilisées dans le projetANR CoSAC, deux stratégies permettant la gestion d’un désherbage de précision sont présentées : 1)un système de pulvérisation localisée, basé sur une solution commerciale, qui permet de détecter etd’appliquer le produit herbicide, en un seul passage ; 2) un système de pulvérisation basé sur laconstruction d’une carte de présence d’adventice, utilisable a posteriori pour contrôler l’ouverture et lafermeture des tronçons de rampe d’un pulvérisateur.Enfin, la durabilité et l’efficacité de ce type de désherbage sont évaluées à l’aide du modèle de « parcellevirtuelle » FLORSYS qui simule le développement des adventices et cultures en fonction du système deculture et de la météo

Drivers-Inspired Ants for Solving the Vehicle Routing Problem with Time Windows

International audienceIn our study, we develop a method that merges two information sources within ants colony optimization heuristic. Namely artificial ants which occurs for short term optimization and transporter's vehicles that occurs in long term and continuous optimization toward solving the real-world vehicle routing problem. This study is supported by a transporter (Upsilon) of the region of l'Yonne in France and a transport and logistics software development company (Tedies). Our method suits for transporters that use human planners to make decisions about their tours and intending to move to computer planners without drastically upsetting the drivers habits. Hence, the pledge of this study is to take advantage from transport operators practices to achieve solutions which are as close as possible to the real-world vehicle routing planning, and keep a human control on the way optimal paths are computed and applied