ABSTRACT
Background The phase III CheckMate 816 study demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) with neoadjuvant N + C vs C in patients (pts) with resectable NSCLC. Here, we report 3-y efficacy, safety, and exploratory biomarker analyses from CheckMate 816. Methods Adults with stage IB (tumors >=4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS <= 1, and no known EGFR/ALK alterations were randomized to N 360 mg + C Q3W or C alone Q3W for 3 cycles followed by surgery. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumor samples. Results At a median follow-up of 41.4 mo (database lock, Oct 14, 2022), continued EFS benefit was observed with N + C vs C (HR, 0.68;95% CI, 0.49-0.93);3-y EFS rates were 57% and 43%, respectively. N + C improved EFS vs C in pts who had surgery, regardless of surgical approach or extent of resection, and in pts with R0 resection (table). Recurrence occurred in 28% and 42% of pts who had surgery in the N + C (n = 149) and C arms (n = 135), respectively. In the N + C arm, BL 4-gene inflammatory signature scores were numerically higher in pts with pCR vs pts without, and EFS was improved in pts with high vs low scores (data to be presented). Grade 3-4 treatment-related and surgery-related adverse events occurred in 36% and 11% of pts in the N + C arm, respectively, vs 38% and 15% in the C arm. Conclusions Neoadjuvant N + C continues to provide long-term clinical benefit vs C in pts with resectable NSCLC, regardless of surgical approach or extent of resection. Exploratory analyses in pts treated with N + C suggested that high BL tumor inflammation may be associated with improved EFS and pCR. Clinical trial identification NCT02998528. Editorial acknowledgement Medical writing and editorial support for the development of this , under the direction of the authors, was provided by Adel Chowdhury, PharmD, Samantha Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb. Legal entity responsible for the study Bristol Myers Squibb. Funding Bristol Myers Squibb. Disclosure P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface;Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus, Kyowa, Novartis, Regeneron;Financial Interests, Personal, Other, Trial steering committee member: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus;Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation;Non-Financial Interests, Personal, Advisory Role, Scientific advisory board member: LUNGevity Foundation. J. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, CLS Therapeutics, Merck, Protalix Biotherapeutics, Roche;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Protalix Biotherapeutics, Regeneron, Roche, Xenetic Biosciences;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, PeerView;Non-Financial Interests, Personal, Other, Data safety monitoring board member: Deutsche Forschungsgemeinschaft;Non-Financial Interests, Personal, Leadership Role, Industry chair: Canadian Association of Thoracic Surgeons. [Formula presented] N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Tak da, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Personal, Other, Family member is an employee: AstraZeneca. M. Provencio: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, Takeda. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Roche, Simcere, ZaiLab;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Hanosh, Roche. M. Awad: Financial Interests, Personal, Other, Consulting fees: ArcherDX, Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Maverick, Merck, Mirati, Nektar, NextCure, Novartis, Syndax;Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Genentech, Eli Lilly. T. Mitsudomi: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, BridgeBio Pharma;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, MSD, Novartis, Ono, Pfizer;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant, Invitae, Merck, MSD, Novartis, Ono, Pfizer, Taiho;Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Leadership Role, Former president: IASLC. E. Felip: Financial Interests, Institutional, Research Grant: Fundacion Merck Salud, Merck KGAa;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, MSD, Novartis, Peptomyc, Pfizer, Sanofi, Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck, MSD, PeerVoice, Pfizer, Sanofi, Takeda, touchONCOLOGY;Non-Financial Interests, Personal, Member of the Board of Directors: Grifols. S.J. Swanson: Financial Interests, Personal, Speaker's Bureau: Ethicon. F. Tanaka: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Taiho;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Chugai, Ono;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Covidien, Eli Lilly, Intuitive, Johnson & Johnson, Kyowa Kirin, MSD, Olympus, Ono, Pfizer, Stryker, Taiho, Takeda. P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb;Financial Interests, Personal, Other, Travel support for attending meetings and travel: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Other, patents planned, issued, or pending: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.R. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by E sevier Inc.
ABSTRACT
During the COVID-19 pandemic, governments have struggled to devise strategies to slow down the spread of the virus. This struggle happens because pandemics are complex scenarios with many unknown variables. In this context, simulated models are used to evaluate strategies for mitigating this and future pandemics. This paper proposes a simulator that analyses small communities by using real geographical data to model the road interactions and the agent's behaviors. Our simulator consists of three different modules: Environment, Mobility, and Infection module. The environment module recreates an area based on map data, including houses, restaurants, and roads. The mobility module determines the agents' movement in the map based on their work schedule and needs, such as eating at restaurants, doing groceries, and going to work. The infection module simulates four cases of infection: on the road, at home, at a building, and off the map. We simulate the surrounding areas of the University of Tsukuba and design three intervention strategies, comparing them to a scenario without any intervention. The interventions are: 1) PCR testing and self-isolation if positive;2) applying lockdown measures to restaurants and barbershops 3) closing grocery stores and restaurants and providing delivery instead. For all scenarios, we observe two areas where most infection happens: hubs, where people from different occupations can meet (e.g., restaurants), and non-hubs, where people with the same occupation meet (e.g., offices). The simulations show that most interventions reduce the total number of infected agents by a large margin. We observed that interventions targeting hubs (2-4) did not impact the infection at non-hubs. In addition, the intervention targeting people's behavior (1) ended up creating a cluster at the testing center. © 2022 International Foundation for Autonomous Agents and Multiagent Systems (www.ifaamas.org). All rights reserved
ABSTRACT
Background: In December Of 2019, Coronavirus Disease 2019 (Covid-19) Emerged In Wuhan. The Government Of Japan Declared A “State Of Emergency” On April 16, 2020. Although This Approach Was Partially Successful For Temporarily Stopping The Spread, Concerns Were Raised Regarding The Negative Impact Of These Measures, Not Only In Terms Of Economics, But Also In Terms Of Mental And Physical Health, Such As Anxiety And Depression. Inflammatory Bowel Diseases (Ibd) Are Intestinal Disorders Affected By Environmental Factors, Such As Sleep, Stress, Diet, And Smoking. Therefore, This Study Aimed To Assess The Effects Of The Covid-19 Pandemic And State Of Emergency On The Lifestyle And Disease Activity Of Patients With Ibd. Methods: We Conducted A Questionnaire Survey In Ibd Patients With Regular Follow-Up At Osaka City University Hospital In Japan, From June 16 To August 21, 2020. The Questionnaire Included Questions Regarding The Patient’S Epidemiological History Of Covid-19, Demographic Data, Gastrointestinal Symptoms, Lifestyle Changes And Stress Related To The State Of Emergency, And Current Medication Use. Gastrointestinal Symptoms Were Assessed Before And During The State Of Emergency Using The 6-Point Mayo Score9 And Patient-Reported Outcome 2 (Pro2) Score10 For Ulcerative Colitis (Uc) And Crohn’S Disease (Cd), Respectively. Results: Overall, 451 Patients Completed The Survey. Patients With Exacerbated Uc Tended Have Younger Age, Less Sleep, And More Stress Against Covid-19 Than Did Patients With Non-Exacerbated Uc. Figure 1 Summarizes The Lifestyle Changes And Stress Related To The State Of Emergency. Patients With Exacerbated Uc Tended Have Younger Age, Less Sleep, And More Stress Against Covid-19 Than Did Patients With Non-Exacerbated Uc. Multivariate Logistic Regression Analysis Identified Younger Age (Odds Ratio [Or] 1.020, 95% Confidence Interval [Ci] 1.010-1.040;P = 0.011), Fewer Sleep Hours (Or 1.320, 95% Ci 1.020-1.720;P = 0.035), And Increased Stress Due To The Covid-19 Pandemic (Or 5.530, 95% Ci 1.650-18.500;P < 0.01) As Independent Risk Factors Associated With Uc Exacerbation During The State Of Emergency. Patients With Exacerbated Cd Had Younger Age At Cd Onset And Had Higher Pro2 Scores Before The State Of Emergency Than Did Patients With Non-Exacerbated Cd. On Multivariate Analysis, Only Younger Age (Or 1.030, 95% Ci 1.010-1.05;P < 0.01) Was Independently Associated With Exacerbation During The State Of Emergency. Conclusions: We Have Showed Data On The Association Between Ibd Activity And Lifestyle Changes / Psychological Stress Due To The State Of Emergency During The Covid-19 Pandemic. This Study Suggests That Improving Sleep Quality And Preventing Psychological Stress Might Be Key In Ibd Management During The Pandemic, Especially In Young Patients. (Figure Presented) (Figure Presented) (Figure Presented) (Figure Presented)