Lancet Respiratory Medicine最新文献

{"title":"Augmenting clinical trials in asthma through digital technology, decentralised designs, and person-centric endpoints: opportunities and challenges","authors":"Job F M van Boven, Richard W Costello, Kit C B Roes, Guy G Brusselle, Kjeld Hansen, Jerry A Krishnan, Christopher E Brightling, Nicolas Roche, Salman Siddiqui, Bruce J Kirenga, Hilary Pinnock, Amy H Y Chan","doi":"10.1016/s2213-2600(24)00327-8","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00327-8","url":null,"abstract":"Digital technologies (eg, smart inhalers, wearables, and sensors) allow for remote, objective, granular, and non-invasive data collection, making them attractive for research evaluating interventions in airways diseases with variable trajectories, such as asthma. Such technologies offer the opportunity to move towards decentralised clinical trials that are done partly or fully outside the classic clinical trial setting and are characterised by remote data collection and monitoring. This approach to evaluating clinical, pharmacological, or behavioural interventions could facilitate recruitment of inclusive and generalisable study populations, enhance personalisation and sustainability, reduce research costs, and accelerate the timeline to novel asthma treatments' market access. This Personal View discusses the application of digital technologies and endpoints within trials; the concept of hybrid and decentralised designs; describes a fully decentralised trial in asthma; and explores the strengths, weaknesses, opportunities, and threats regarding their implementation from the clinician, patient expert, low-resource, and regulator viewpoints.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"13 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time to escalate quality assurance in small-cell lung cancer radiotherapy trials","authors":"Gerard M Walls, Marcel van Herk, Corinne Faivre-Finn","doi":"10.1016/s2213-2600(24)00338-2","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00338-2","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"29 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time to escalate quality assurance in small-cell lung cancer radiotherapy trials – Authors' reply","authors":"Jiayi Yu, Jun Zhao, Anhui Shi","doi":"10.1016/s2213-2600(24)00335-7","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00335-7","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"12 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An unusual pulmonary complication of smoking","authors":"Felix Chua, Josien van Es, Rainer Doffinger, Tom Pickworth, Bart Koopman, Bekir Karakaya, Marcel Veltkamp, Maria Kokosi","doi":"10.1016/s2213-2600(24)00268-6","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00268-6","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Contributors</h2>FC conceptualised the study, provided clinical care, was involved in data collection and interpretation, and wrote the first draft of the report. JvE, TP, BKo, BKa, MV, and MK were involved in clinical care, data collection, and interpretation and contributed to the writing of the report. RD performed assays, interpreted data, and contributed to the writing of the report.</section></section><section><section><h2>Declaration of interests</h2>We declare no competing interests.</section></section><section><section><h2>Acknowledgments</h2>The project was supported by the Royal Brompton Hospital (London, UK), Onze Lieve Vrouwe Gasthuis (OLVG) Hospital (Amsterdam, Netherlands), Cambridge University Hospitals NHS Foundation Trust (Cambridge, UK), and St Antonius Hospital (Nieuwegein, Netherlands). The views expressed in this publication are those of the authors and not necessarily those of the NHS or the Dutch health system.</section></section>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"85 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Margareth Dalcolmo: TB expert and Brazil's “face of COVID-19”","authors":"Tony Kirby","doi":"10.1016/s2213-2600(24)00378-3","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00378-3","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"223 3 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the indication of CFTR modulator combinations for people with cystic fibrosis with non-F508del variants.","authors":"Pierre-Régis Burgel","doi":"10.1016/S2213-2600(24)00249-2","DOIUrl":"10.1016/S2213-2600(24)00249-2","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"934-935"},"PeriodicalIF":38.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Savolitinib in NSCLC: progress in the MET exon 14 journey.","authors":"Tetsuya Mitsudomi","doi":"10.1016/S2213-2600(24)00258-3","DOIUrl":"10.1016/S2213-2600(24)00258-3","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"936-937"},"PeriodicalIF":38.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of elexacaftor-tezacaftor-ivacaftor treatment in individuals with cystic fibrosis and CFTR^N1303K in the USA: a prospective, multicentre, open-label, single-arm trial.","authors":"George M Solomon, Rachel W Linnemann, Rachel Rich, Ashleigh Streby, Brian Buehler, Eric Hunter, Kadambari Vijaykumar, William R Hunt, John J Brewington, Andras Rab, Shasha P Bai, Adrianna L Westbrook, Carmel McNicholas-Bevensee, Jong Hong, Candela Manfredi, Cristina Barilla, Shingo Suzuki, Brian R Davis, Eric J Sorscher","doi":"10.1016/S2213-2600(24)00205-4","DOIUrl":"10.1016/S2213-2600(24)00205-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;CFTR modulators are approved for approximately 90% of people with cystic fibrosis in the USA and provide substantial clinical benefit. N1303K (Asn1303Lys), one of the most common class 2 CFTR defects, has not been approved for these therapies by any regulatory agency. Preclinical investigation by our laboratories showed N1303K CFTR activation with elexacaftor-tezacaftor-ivacaftor (ETI). In this trial, we evaluate whether ETI improves CFTR function, measured by sweat chloride and other clinical outcomes, in people with cystic fibrosis and CFTR&lt;sup&gt;N1303K&lt;/sup&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this prospective, open-label, single-arm trial, participants aged 12 years or older with cystic fibrosis encoding at least one N1303K variant and at least one CFTR&lt;sup&gt;N1303K&lt;/sup&gt; allele who were ineligible for modulator therapy by US Food and Drug Administration labelling were given ETI for 28 days followed by a 28-day washout period at two cystic fibrosis centres in the USA. Participants received two orally administered pills of 100 mg elexacaftor, 50 mg tezacaftor, and 75 mg ivacaftor once daily in the morning, and 150 mg ivacaftor once daily in the evening. The primary endpoint was mean change in sweat chloride from baseline up to day 28 compared with mixed-effects models. Secondary endpoints were changes in percentage of predicted FEV&lt;sub&gt;1&lt;/sub&gt; (ppFEV&lt;sub&gt;1&lt;/sub&gt;), Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain, BMI, and weight after ETI therapy. Safety was assessed in all participants who received at least one dose of the study drug and primary and secondary analyses were performed in all participants who took the study drug per protocol. The trial was registered at ClinicalTrials.gov (NCT03506061) and remains open for reporting purposes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between June 7, 2022, and Oct 20, 2023, 20 participants (ten male and ten female) were enrolled and received ETI treatment. One participant was lost to follow-up but was included in intention-to-treat analyses. At 28 days, the mean sweat chloride reduction was -1·1 mmol/L (95% CI -5·3 to 3·1; p=0·61) with only one participant showing a sweat chloride decrease greater than 15 mmol/L. There was a mean increase in ppFEV&lt;sub&gt;1&lt;/sub&gt; from baseline at day 28 of 9·5 percentage points (6·7-12·3; p&lt;0·0001) with 15 (75%) participants showing at least a 5% increase in ppFEV&lt;sub&gt;1&lt;/sub&gt;. Improvements were also identified in mean CFQ-R respiratory domain score (20·8 increase [95% CI 11·9-29·8]; p&lt;0·0001), BMI (0·4 kg/m&lt;sup&gt;2&lt;/sup&gt; increase [0·2-0·7]; p=0·0017), and weight (1·0 kg increase [0·4-1·7]; p=0·0020) after 28 days of ETI treatment. 14 (70%) of 20 participants had adverse events (12 [60%] mild, one [5%] moderate), with one (5%) serious adverse event of hospitalisation attributed to pneumonia. No deaths were recorded in the study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Individuals with CFTR&lt;sup&gt;N1303K&lt;/sup&gt; showed no change in sweat chlo","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"947-957"},"PeriodicalIF":38.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study.","authors":"Yongfeng Yu, Qisen Guo, Yongchang Zhang, Jian Fang, Diansheng Zhong, Baogang Liu, Pinhua Pan, Dongqing Lv, Lin Wu, Yanqiu Zhao, Juan Li, Zhihua Liu, Chunling Liu, Haichuan Su, Yun Fan, Tongmei Zhang, Anwen Liu, Bo Jin, Ye Wang, Jianying Zhou, Zhihong Zhang, Fengming Ran, Xia Song, Michael Shi, Weiguo Su, Shun Lu","doi":"10.1016/S2213-2600(24)00211-X","DOIUrl":"10.1016/S2213-2600(24)00211-X","url":null,"abstract":"<p><strong>Background: </strong>Savolitinib has been approved in China for advanced or metastatic non-small-cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations in previously treated patients and those unable to receive platinum-based chemotherapy. We report results from a treatment-naive cohort of a phase 3b study that was designed to evaluate the efficacy and safety of savolitinib in locally advanced or metastatic METex14-mutated NSCLC.</p><p><strong>Methods: </strong>This single-arm, multicohort, multicentre, open-label, phase 3b study was done at 48 hospitals in China in adult (≥18 years) patients with locally advanced or metastatic METex14-mutated NSCLC who had not received previous systemic antitumour therapy. Patients with a bodyweight of 50 kg or more and those with a bodyweight of less than 50 kg received savolitinib once daily at 600 mg or 400 mg, respectively, in 21-day cycles. The primary endpoint was objective response rate assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumours, version 1.1. The full analysis set comprised all patients who received at least one dose of study medication, which was used to assess the efficacy endpoints and baseline and safety data. This study is registered with ClinicalTrials.gov (NCT04923945) and is closed to accrual.</p><p><strong>Findings: </strong>Between Aug 31, 2021, and Oct 20, 2023, 125 treatment-naive patients were assessed for eligibility, of whom 87 were enrolled and received savolitinib. The median age of patients was 70·0 years (IQR 65·2-75·8) and 51 (59%) of 87 patients were male and 36 (41%) were female. In the full analysis set, the IRC-assessed objective response rate was 62% (95% CI 51-72) and the investigator-assessed objective response rate was 60% (49-70), showing a high concordance rate (84%). Treatment-related adverse events were reported in 85 (98%) of 87 patients, with peripheral oedema (54 [62%]) being the most common. Two of these treatment-related adverse events led to death (cardiac failure n=1, unknown reasons n=1).</p><p><strong>Interpretation: </strong>Savolitinib showed manageable toxicity and promising efficacy in treatment-naive patients with advanced or metastatic METex14-mutated NSCLC.</p><p><strong>Funding: </strong>HUTCHMED and AstraZeneca.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"958-966"},"PeriodicalIF":38.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic body radiotherapy plus neoadjuvant chemoimmunotherapy in operable non-small-cell lung cancer.","authors":"Rafał Dziadziuszko, Bartłomiej Tomasik","doi":"10.1016/S2213-2600(24)00289-3","DOIUrl":"10.1016/S2213-2600(24)00289-3","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"941-943"},"PeriodicalIF":38.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}