Brief Report: Updated Data From IMscin001 Part 2, a Randomized Phase III Study of Subcutaneous Versus Intravenous Atezolizumab in Patients With Locally Advanced/Metastatic NSCLC.

INTRODUCTION: Subcutaneous atezolizumab is approved for the treatment of various solid tumors. Previous results from the IMscin001 study (NCT03735121) demonstrated that the pharmacokinetics, efficacy, immunogenicity, and safety of subcutaneous and intravenous atezolizumab were consistent (data cutoff: April 26, 2022). We present updated data from this trial (data cut-off: 16 January 2023). METHODS: Eligible patients aged ≥18 years with locally advanced/metastatic NSCLC were randomized (2:1) to receive atezolizumab subcutaneously (1875 mg, n=247) or intravenously (1200 mg, n=124) every 3 weeks. Here we present updated efficacy (overall survival [OS]; progression-free survival; objective response rate; duration of response), safety, and immunogenicity endpoints, alongside patient-reported outcomes (PROs) and healthcare practitioner (HCP) perspectives. RESULTS: In this updated analysis, the median survival follow-up was 9.5 months. Median subcutaneous injection time was 7.1 minutes, with an average subcutaneous injection time of 4-8 minutes in most patients (75.7%). OS data were mature: median OS was similar between treatment arms, at 10.7 and 10.1 months in the subcutaneous and intravenous arms, respectively (HR: 0.88; 95% CI: 0.67-1.16). Other efficacy endpoints, as well as immunogenicity, PROs, and safety, were similar between arms. Most HCPs found subcutaneous administration convenient (79.5%), easy to administer (89.7%), and were satisfied with the treatment (84.6%); 75.0% of HCPs agreed that administering atezolizumab subcutaneously compared with intravenously could save time. CONCLUSIONS: In this analysis, mature OS data were similar between treatments. The updated efficacy and safety profile of subcutaneous atezolizumab is consistent with previous findings and equivalent to intravenous atezolizumab.

Assessing the impact of digital patient monitoring on health outcomes and healthcare resource usage in addition to the feasibility of its combination with at-home treatment, in participants receiving systemic anticancer treatment in clinical practice: protocol for an interventional, open-label, multicountry platform study (ORIGAMA).

INTRODUCTION: Digital patient monitoring (DPM) tools can enable more effective clinical care and improved patient outcomes in cancer. However, their broad adoption requires ease of use and demonstration of real-world clinical utility/impact. ORIGAMA (MO42720) is an interventional, open-label, multicountry platform study investigating the clinical utility of DPM tools and specific treatments. ORIGAMA will begin with two cohorts that aim to assess the impact of the atezolizumab-specific Roche DPM Module (hosted on the Kaiku Health DPM platform (Helsinki, Finland)) on health outcomes and healthcare resource usage, and its feasibility to support at-home treatment administration, in participants receiving systemic anticancer treatment. Other digital health solutions may be added to future cohorts. METHODS AND ANALYSIS: In Cohort A, participants with metastatic non-small cell lung cancer (NSCLC), extensive-stage SCLC or Child Pugh A unresectable hepatocellular carcinoma will be randomised to a locally approved anticancer regimen containing intravenous atezolizumab (TECENTRIQ, F. Hoffmann-La Roche Ltd/Genentech) and local standard-of-care support, with/without the Roche DPM Module. Cohort B will assess the feasibility of the Roche DPM Module in supporting administration of three cycles of subcutaneous atezolizumab (1875 mg; Day 1 of each 21-day cycle) in the hospital, followed by 13 cycles at home by a healthcare professional (ie, flexible care), in participants with programmed cell-death ligand 1-positive, early-stage NSCLC. The primary endpoints are the mean difference in change of the participant-reported Total Symptom Interference Score at Week 12 from baseline (Cohort A) and flexible care adoption rate at Cycle 6 (Cohort B). ETHICS AND DISSEMINATION: This study will be conducted according to the Declaration of Helsinki, and/or the applicable laws and regulations of the country in which the research is conducted, whichever affords the greater protection to the individual. The study received its first Ethics Committee approval in Spain in October 2022. Participants will provide written informed consent in a face-to-face setting. The results of this study will be presented at national and/or international congresses and disseminated via publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05694013.

Systematic literature review of methodologies and data sources of existing economic models across the full spectrum of Alzheimer's disease and dementia from apparently healthy through disease progression to end of life care: a systematic review protocol.

INTRODUCTION: Dementia is one of the greatest health challenges the world will face in the coming decades, as it is one of the principal causes of disability and dependency among older people. Economic modelling is used widely across many health conditions to inform decisions on health and social care policy and practice. The aim of this literature review is to systematically identify, review and critically evaluate existing health economics models in dementia. We included the full spectrum of dementia, including Alzheimer's disease (AD), from preclinical stages through to severe dementia and end of life. This review forms part of the Real world Outcomes across the Alzheimer's Disease spectrum for better care: multimodal data Access Platform (ROADMAP) project. METHODS AND ANALYSIS: Electronic searches were conducted in Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Economic Literature Database, NHS Economic Evaluation Database, Cochrane Central Register of Controlled Trials, Cost-Effectiveness Analysis Registry, Research Papers in Economics, Database of Abstracts of Reviews of Effectiveness, Science Citation Index, Turning Research Into Practice and Open Grey for studies published between January 2000 and the end of June 2017. Two reviewers will independently assess each study against predefined eligibility criteria. A third reviewer will resolve any disagreement. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed using the Phillips checklist for decision analytic modelling. A narrative synthesis will be used. ETHICS AND DISSEMINATION: The results will be made available in a scientific peer-reviewed journal paper, will be presented at relevant conferences and will also be made available through the ROADMAP project. PROSPERO REGISTRATION NUMBER: CRD42017073874.

A mathematical model for HIV and hepatitis C co-infection and its assessment from a statistical perspective.

The hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) are a clear threat for public health, with high prevalences especially in high risk groups such as injecting drug users. People with HIV infection who are also infected by HCV suffer from a more rapid progression to HCV-related liver disease and have an increased risk for cirrhosis and liver cancer. Quantifying the impact of HIV and HCV co-infection is therefore of great importance. We propose a new joint mathematical model accounting for co-infection with the two viruses in the context of injecting drug users (IDUs). Statistical concepts and methods are used to assess the model from a statistical perspective, in order to get further insights in: (i) the comparison and selection of optional model components, (ii) the unknown values of the numerous model parameters, (iii) the parameters to which the model is most 'sensitive' and (iv) the combinations or patterns of values in the high-dimensional parameter space which are most supported by the data. Data from a longitudinal study of heroin users in Italy are used to illustrate the application of the proposed joint model and its statistical assessment. The parameters associated with contact rates (sharing syringes) and the transmission rates per syringe-sharing event are shown to play a major role.