Durvalumab (D) +/- tremelimumab (T) + chemotherapy (CT) in 1L metastatic (m) NSCLC: Overall survival (OS) update from POSEIDON after median follow-up (mFU) of approximately 4 years (y)

Background: In the Phase 3 POSEIDON study, 1L T+D+CT demonstrated statistically significant improvements in PFS and OS (OS HR 0.77;95% CI 0.65-0.92;p=0.0030;mFU 34.9 mo in censored pts) vs CT alone in pts with mNSCLC. D+CT showed a statistically significant improvement in PFS and a positive trend for OS improvement vs CT that did not reach significance (OS HR 0.86;95% CI 0.72-1.02;p=0.0758). Here we report an updated exploratory analysis of OS, and histology and mutational status subgroups, after a mFU of ~4 y. Method(s): Pts with EGFR/ALK wild-type mNSCLC were randomised 1:1:1 to 1L D (until progression) +/- limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles);or CT (up to 6 cycles). Alpha-controlled endpoints were PFS and OS for D+CT vs CT and T+D+CT vs CT. Pt tumours were molecularly characterised via sequencing of tissue and/or ctDNA samples. Result(s): At an updated data cutoff (DCO) of 11 Mar 2022 (mFU 46.5 mo in censored pts), T+D+CT continued to show OS benefit vs CT (HR 0.75;95% CI 0.63-0.88) with an estimated 25.0% of pts alive at 3 y vs 13.6% (Table). D+CT continued to numerically improve OS vs CT (HR 0.84;95% CI 0.71-0.99;3 y OS 20.7%). Consistent with results at the earlier DCO, OS benefit appeared more pronounced with T+D+CT vs CT in pts with non-squamous (than squamous;data will be presented) histology. A trend for OS benefit with T+D+CT vs CT continued to be observed in non-squamous subgroups with mutations (m) in STK11 (Table), KEAP1 or KRAS (data will be presented). No new safety signals were identified based on collection of serious AEs during long-term FU. [Formula presented] Conclusion(s): The results of this exploratory analysis from POSEIDON, after mFU of ~4 y, demonstrate the durable long-term OS benefit of adding a limited course of T to D and 4 cycles of CT. These data support the use of this regimen as a 1L treatment option for pts with mNSCLC, including harder-to-treat mutational subgroups such as STK11m, KEAP1m or KRASm. Clinical trial identification: NCT03164616 (release date: 23 May 2017). Editorial acknowledgement: Medical writing support for the development of this , under the direction of the authors, was provided by James Holland, PhD, of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca PLC. Funding(s): AstraZeneca. Disclosure: B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc;Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp., J INTS BIO;Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp, J INTS BIO;Financial Interests, Personal, Royalties: Champions Oncology;Financial Interests, Personal, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp;Financial Interests, Personal, Advisory Role, Consulting: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines;Financial Interests, Personal, Other: DAAN Biotherapeutics. J.A. Alatorre Alexander: Financial Interests, Personal, Speaker's Bureau: BMS, Roche, AstraZeneca, MSD, Boehringer Ingelheim, Takeda, Eli Lilly, Janssen;Financial Interests, Personal, Advisory Board: BMS, Roche, AstraZeneca, MSD, Boehringer Ingelheim, Takeda, Eli Lilly, Janssen. S. Lucien Geater: Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Institutional, Principal Investigator: AstraZeneca, Roche, Novartis, Boehringer Ingelheim;Financial Interests, Personal, Advisory Role: Pfizer. K. Sang-We: Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim;Financial I terests, Personal, Research Grant: Yuhan;Non-Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Boehringer Ingelheim, Norvatis, Lilly, Takeda, Therapex, and Yuhan. M. Hussein: Financial Interests, Personal, Advisory Board: AbbVie, Aptitude Health, AstraZeneca, Biopahrama, BMS, Exelixis, Mirati Therapeutics, Cardinal Health, Coherus Biosciences, Athenex, Karyopharm Therapeutics, IntegraConnect, Oncocyte. C.T. Yang: Financial Interests, Personal, Principal Investigator: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Merck, Amgen, Johnson & Johnson, AbbVie, Hanso Pharma, Roche, Ono, BMS, Chugai. L.H. Araujo: Financial Interests, Personal, Invited Speaker: MSD, Roche, Pfizer, AstraZeneca, Takeda, Lillly, Janssen, Amgen, Novartis, BMS, Sanofi;Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, AstraZeneca, Sanofi. H. Saito: Financial Interests, Personal, Speaker's Bureau: AstraZeneca, ONO Pharmaceutical;Financial Interests, Personal, Principal Investigator: AstraZeneca, Chugai Pharmaceutical ONO Pharmaceutical, Bristol Myers Squibb. N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Hoffmann-La Roche, Janssen, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Other: Symphogen: Data Safety Monitoring Board. Z. Lai, H. Mann, X. Shi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca;Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure;Financial Interests, Institutional, In ited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati;Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier;Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca;Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca;Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS;Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS;Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene;Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK;Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD;Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati;Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar;Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics;Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01;chair ALEX;steering committee BFAST;steering committee BEAT-Meso;steering committee ImPower-030, IMforte: Roche/Genentech;Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos;Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO;Non-Financial Interests, Personal, Officer, Council Me ber & Scientific Committee Chair: ETOP/IBCSG Partners;Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK;Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities;Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Bejart Lausanne Foundation;Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK;Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR;Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO;Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK;Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO;Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. E.B. Garon: Financial Interests, Personal, Advisory Board: ABL Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, Eisai, Eli Lilly, EMD Serono, Gilead, GSK, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, Xilio Therapeutics;Financial Interests, Personal, Research Grant: ABL Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, EMD Serono, Genentech, Iovance Biotherapeutics, Eli Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, Novartis. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, BI, BMS, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communication, Janssen Pharmaceutica NV, Jiahui Holdings Co. Limi, Novartis, OrigiMed Co. Ltd., P. Permanyer SL, PeerVoice, Physicians' Education Resource, Pfizer, PrIME Oncology, Research to Practice, RochePharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd., T;Financial Interests, Personal, Advisory Board: AbbVie Inc., ACEA Pharma, Amgen, AstraZeneca, Berry Oncology, Blueprint Medicines Corporation, Boehringer Ingelheim Pharmaceuticals Inc., Bristol Myers Squibb Company, C4 Therapeutics, Inc, Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lily, Loxo-Oncology Inc., Lunit, Inc., Mer k Serono, Merck Sharp & Dohme, Mirati Therapeutics, Inc., MiRXES Group, Novartis, OrigiMed, Pfizer, Puma Biotechnolo;Financial Interests, Personal, Member of the Board of Directors: AstraZeneca PLC, HutchMed;Financial Interests, Personal, Full or part-time Employment: The Chinese University of Hong Kong (Full-Time);Financial Interests, Personal, Stocks/Shares: Aurora Tele-Oncology Ltd., HutchMed, Act Genomics-Sanomics Group, Loxo-oncology, Virtus Medical Group and Lunit USA, Inc;Non-Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery;Financial Interests, Personal, Leadership Role: Lunit USA, Inc., ACT Genomics-Sanomics Group, Aurora;Financial Interests, Personal, Other, Independent contractor: AbbVie Inc., ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, Berry Oncology, BI, Blueprint Medicines Corporation, BMS, C4 Therapeutics, Inc, CStone Pharmaceuticals, Curio Science, Daiichi Sa, Loxo-Oncology, Merck Serono, MSD, Mirati Therapeutics Inc., MoreHealth, Novartis, OrigiMed, Pfizer, Puma Biotechnology Inc., Qiming Development (HK) Ltd., Roche Pharmaceuticals, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Takeda Pharmaceuticals HK Ltd., Vert, Guardant Health, Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lilly, Lunit USA, Inc., Loxo-Oncology, Lucence Health Inc., Medscape LLC/ WebMD, Merck Serono, MSD, Mirati Therapeutics Inc., MiRXES, MoreHea. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie;Acerta;Adaptimmune;Amgen;Apexigen;Arcus B osciences;Array BioPharma;Artios Pharma;AstraZeneca;Atreca, BeiGene;BerGenBio;BioAtla;Boehringer Ingelheim, Calithera Biosciences;Checkpoint Therapeutics;Corvus Pharmaceuticals;Curis;CytomX, Daiichi Sanyo;Dracen Pharmaceuticals;Dynavax, Eli Lilly, Elicio Therapeutics, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan Kettering, Merck, Merus, Mirati Therapeutics, NeoImmuneTech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Pharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics;Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Eli Lilly, EMD Serono, G1 Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, IDEAYA Biosciences, iTeos, Janssen, Merck, Mirati Therapeutics, Novartis, Oncorus, Regeneron Pharmaceuticals, Revolution Medicines, Ribon Therapeutics, Sanofi, Turning Point Therapeutics, WindMIL. All other authors have declared no conflicts of interest. Copyright © 2022

ENHANCEMENT OF STROKE REHABILITATION WITH LEVODOPA (ESTRELSTUDY) - DESIGN AND PROGRESS OF THE ONGOING MULTICENTER PLACEBOCONTROLLED RANDOMIZED TRIAL

Background: In this multicenter, randomized, placebo-controlled trial we study whether Levodopa given in addition to usual rehabilitative therapies is associated with a patient-relevant enhancement of motor recovery after acute stroke. Methods: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a multicenter, placebo-controlled randomized superiority trial. Patients with an acute ischemic or hemorrhagic stroke ≤7 days leading to a clinically meaningful hemiparesis in need of in-hospital rehabilitation are enrolled in stroke units and later transferred to experienced neurorehabilitation centers. Participants receive Levodopa 100mg/Carbidopa 25mg three times daily or matching placebo for 5 weeks in addition to standardized rehabilitative therapy. The primary outcome is the Fugl-Meyer- Motor Assessment score 3 months after randomization. We present the characteristics of the first 200 of 610 patients to be enrolled. Results: 13 certified stroke units and 13 neurorehabilitation centers are involved (“stroke-pathway-trial”). The first 200 participants had a median age of 73 [IQR 64-82] years and 43.5 % were female. 169 patients (84.5%) had ischemic stroke. At baseline, the median NIH-Stroke scale score was 8 [5-10]. Successful 3-month assessment was performed in 183 patients (91.5%);11 (5%) died, 5 (2.5%) withdrew from the study and 1 patient missed the clinical 3 months-visit due to the COVID-19 pandemic. Conclusions: The ESTREL study will provide evidence whether the additional use of Levodopa in the rehabilitation process of stroke patients is safe and effective. The ESTREL-study started successfully due to the good cooperation between acute stroke units and rehabilitation centers, as well as the high acceptance rate among patients.

Ischemic stroke in consecutive patients with COVID-19: A case-control study of clinical features, mechanisms and outcome in the swiss stroke registry

Background and Aims: Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to random centers or lack 3-month outcome. The aim of this study is to describe prevalence, clinical, radiological and pathophysiological features and long-term outcome of COVID-19-related IS in a nationwide stroke registry. Methods: From the Swiss Stroke Registry (SSR), we included all consecutive IS patients aged ≥18 years who were admitted to stroke units during the first wave of COVID-19 (25.02.-08.06.2020). We compared baseline features, stroke etiology and 3-month outcome (modified Rankin shift) of COVID PCR+ IS patients with COVID PCR-and/or asymptomatic non-tested IS patients. Results: Of the 2376 IS patients entered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection (details in Figure 1). In multivariate analysis, COVID+ patients had lower admission blood pressure (p=0.004) and more frequently lesions in multiple vascular territories (p=0.09). Stroke seemed more often related to several defined etiologies (p=0.07), and less often to large artery atherosclerotic (p=0.07) and cryptogenic mechanisms (p=0.03). There was a strong trend towards worse outcome in COVID+ patients across the entire Rankin-spectrum (Figure 2) despite adjustment for age, stroke severity and revascularization treatments (OR 1.97, 95%CI 0.92-4.21, p=0.08). Conclusions: In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multiple territory involvement and multiple stroke mechanisms, and their 3-month outcome was worse across the entire Rankin spectrum. (Table Presented).

How do we fight COVID-19? Military medical actions in the war against the COVID-19 pandemic in France.

'We are at war', French President Emmanuel Macron said in an address to the nation on 16 March 2020. As part of this national effort, the French Military Medical Service (FMMS) is committed to the fight against COVID-19. This original report aimed to describe and detail actions that the FMMS has carried out in the nationwide fight against the COVID-19 pandemic in France, as well as overseas. Experts in the field reported major actions conducted by the FMMS during the COVID-19 pandemic in France. In just few weeks, the FMMS developed ad hoc medical capabilities to support national health authorities. It additionally developed adaptive, collective en route care via aeromedical and naval units and deployed a military intensive care field hospital. A COVID-19 crisis cell coordinated the French Armed Forces health management. The French Military Centre for Epidemiology and Public Health provided all information needed to guide the decision-making process. Medical centres of the French Armed Forces organised the primary care for military patients, with the widespread use of telemedicine. The Paris Fire Brigade and the Marseille Navy Fire Battalion emergency departments ensured prehospital management of patients with COVID-19. The eight French military training hospitals cooperated with civilian regional health agencies. The French military medical supply chain supported all military medical treatment facilities in France as well as overseas, coping with a growing shortage of medical equipment. The French Armed Forces Biomedical Research Institute performed diagnostics, engaged in multiple research projects, updated the review of the scientific literature on COVID-19 daily and provided expert recommendations on biosafety. Finally, even students of the French military medical academy volunteered to participate in the fight against the COVID-19 pandemic. In conclusion, in an unprecedented medical crisis, the FMMS engaged multiple innovative and adaptive actions, which are still ongoing, in the fight against COVID-19. The collaboration between military and civilian healthcare systems reinforced the shared objective to achieve the goal of 'saving the greatest number'.