Lancet Respiratory Medicine最新文献

{"title":"Estimated worldwide variation and trends in incidence of lung cancer by histological subtype in 2022 and over time: a population-based study","authors":"Ganfeng Luo, Yanting Zhang, Harriet Rumgay, Eileen Morgan, Oliver Langselius, Jerome Vignat, Murielle Colombet, Freddie Bray","doi":"10.1016/s2213-2600(24)00428-4","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00428-4","url":null,"abstract":"<h3>Background</h3>Lung cancer is the most common cancer worldwide, yet the current epidemiological profile of lung-cancer incidence by histological subtype is only partly understood. We aimed to assess geographical variation in incidence of lung cancer by subtype worldwide in 2022, geographical variation in adenocarcinoma incidence attributable to ambient particulate matter (PM) pollution worldwide in 2022, temporal trends in lung-cancer incidence by subtype from 1988 to 2017 in 19 countries, and generational changes.<h3>Methods</h3>For this population-based study, we used data from the Global Cancer Observatory (GLOBOCAN) 2022, <em>Cancer Incidence in Five Continents Volumes VII–XII</em>, and members of the African Cancer Registry Network. To obtain national estimates of lung cancer in 2022 for the four main histological subtypes (ie, adenocarcinoma, squamous cell carcinoma [SCC], small-cell carcinoma, and large-cell carcinoma) by year, sex, and age group, we combined national estimates with representative, subsite-specific incidence proportions of lung cancer on the basis of recorded incidence data compiled in <em>Cancer Incidence in Five Continents Volume XII</em> and from members of the African Cancer Registry Network. We calculated country-specific, sex-specific, and age-specific proportions of and sex-specific and age-specific incidence rates per 100 000 people for all four histological subtypes. To account for differences in age composition between populations by country, we calculated age-standardised incidence rates (ASRs) per 100 000 people for lung cancer by subtype and sex at national and regional levels. We also quantified the burden of adenocarcinoma incidence attributable to ambient PM pollution for 179 countries in 2022. We conducted joinpoint regression and age-period-cohort analysis to assess temporal trends in ASRs in 19 countries by sex.<h3>Findings</h3>In 2022, we estimated that there were 1 572 045 new cases of lung cancer worldwide among male individuals, of which 717 211 (45·6%) were adenocarcinoma, 461 171 (29·4%) were SCC, 180 063 (11·5%) were small-cell carcinoma, and 101 861 (6·5%) were large-cell carcinoma. In 2022, we estimated that there were 908 630 new cases of lung cancer worldwide among female individuals, of which 541 971 (59·7%) were adenocarcinoma, 155 598 (17·1%) were SCC, 87 902 (9·7%) were small-cell carcinoma, and 59 271 (6·5%) were large-cell carcinoma. Among male individuals, the highest ASRs were in east Asia for adenocarcinoma (27·12 [95% CI 27·04–27·21] per 100 000 people), east Europe for SCC (21·70 [21·51–21·89] per 100 000 people) and small-cell carcinoma (9·85 [9·72–9·98] per 100 000 people), and north Africa for large-cell carcinoma (4·33 [4·20–4·45] per 100 000 people). Among female individuals, the highest ASRs were in east Asia for adenocarcinoma (19·04 [18·97–19·11] per 100 000 people), north America for SCC (5·28 [5·21–5·35] per 100 000 people) and small-cell carcinoma (4·28 [4·21–4·35] pe","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"20 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083494","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":"Rezivertinib versus gefitinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (REZOR): a multicentre, double-blind, randomised, phase 3 study","authors":"Yuankai Shi, Yanzhen Guo, Xingya Li, Lin Wu, Zhaohong Chen, Sheng Yang, Minghong Bi, Yanqiu Zhao, Wenxiu Yao, Huiqing Yu, Ke Wang, Wenhua Zhao, Meili Sun, Liangming Zhang, Zhiyong He, Yingcheng Lin, Jianhua Shi, Bo Zhu, Lijun Wang, Yueyin Pan, Anqi Zhou","doi":"10.1016/s2213-2600(24)00417-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00417-x","url":null,"abstract":"<h3>Background</h3>This study aimed to compare the efficacy and safety of rezivertinib (BPI-7711) and gefitinib as first-line therapies in patients with <em>EGFR</em>-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC).<h3>Methods</h3>This multicentre, double-blind, randomised, phase 3 study (REZOR) included eligible patients from 50 hospitals across China. Those who had been histologically or cytologically confirmed as having NSCLC with <em>EGFR</em> exon 19 deletion or exon 21 Leu858Arg mutation by central laboratory were randomly assigned (1:1) to receive once daily either rezivertinib 180 mg or gefitinib 250 mg, until unacceptable toxicity occurred, disease progression, or other treatment discontinuation criteria were met. Each cycle lasted for 21 days. The primary endpoint was progression-free survival evaluated by masked independent central review (MICR) in the intention-to-treat set. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03866499</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> and follow-up is ongoing.<h3>Findings</h3>Between July 15, 2019, and Feb 14, 2022, 695 patients were screened. Among them, 369 eligible patients were randomly assigned to receive either rezivertinib 180 mg/day plus placebo (n=184) or gefitinib 250 mg/day plus placebo (n=185) in a 1:1 ratio; all of eligible participants were included in the intention-to-treat set. Median MICR-assessed progression-free survival was 19·3 months (95% CI 13·8–22·1) in the rezivertinib group and 9·6 months (8·4–11·3) in the gefitinib group (hazard ratio [HR] 0·48, 95% CI 0·36–0·63; p<0·0001) and the prespecified subgroup efficacy analysis showed consistent results. Median duration of exposure was 16·0 months (95% CI 0·0–29·7) in the rezivertinib group and 11·0 months (0·0–28·9) in the gefitinib group. Grade 3 or higher treatment-emergent adverse events (82 [45%] of 184 in the rezivertinib group; 80 [43%] of 185 in the gefitinib group) and treatment-related adverse events (TRAEs; 43 [23%] of 184 in the rezivertinib group; 43 [23%] of 185 in the gefitinib group) were similar in both groups. One patient died from a TRAE in the rezivertinib group, due to pneumonia and interstitial lung disease.<h3>Interpretation</h3>Our findings suggested that rezivertinib is a potential choice for patients with <em>EGFR</em>-mutated locally advanced or metastatic NSCLC as first-line therapy, owing to the superior overall efficacy and subgroup progression-free survival compared with gefitinib in targeted patients. No new safety signals were identified.<h3>Funding</h3>Beta Pharma","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"61 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083492","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":"Chronic obstructive pulmonary disease: new therapies and old needs","authors":"Nicholas S Hopkinson","doi":"10.1016/s2213-2600(24)00423-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00423-5","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"37 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072379","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":"Marcel Proust (1871–1922): a historico-medical review of his fatal asthma","authors":"Donatella Lippi, Elena Varotto, Francesco M Galassi, Francesco Baldanzi","doi":"10.1016/s2213-2600(25)00013-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00013-x","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>The historico-medical context</h2>Marcel Proust's medical conditions have been widely studied, with detailed reconstruction of the history of his illness and the influence it had on his artistic production. Proust had recurrent attacks of severe asthma from the age of 9 years, later developing an obstructive lung disease, before dying of infectious pneumonia at the age of 51 years.Marcel Proust grew up in a family of doctors and had the availability of personal acquaintances and medical texts from which to draw information: his</section></section><section><section><h2>Asthma, <em>meditatio mortis</em></h2>One of the most accurate descriptions of asthma by today's standards was that of <span><span>John Floyer</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (1649–1734), a physician and polyhistor, himself suffering from asthma, who had defined the disease, separating it from other pulmonary disorders and recognising its hereditary nature. He identified the cause of dyspnoea in bronchial constriction, due to spasm, considering tonic spasm more like catalepsy than the clonic convulsion of epilepsy. According to Floyer, periodic asthma, understood as</section></section><section><section><h2>Marcel Proust's disease</h2>Proust had suffered his first asthma attack at the age of 9 years. Subsequently, his asthma had worsened, and he had been visited by numerous doctors. However, the only doctor who took care of Proust during the last 20 years of his life was Maurice Bize, a family doctor who visited him faithfully every Friday from 1904 onwards until his death.Proust's asthma was probably a common and severe form of bronchial asthma associated with allergies and hay fever. The non-respiratory manifestations</section></section><section><section><h2>Neurologists at Proust's bedside</h2>As asthma was considered a nervous disease, it is not surprising that the most famous doctors consulted by Proust were neurologists or neuropsychiatrists. Proust consulted Joseph Babinski (1857–1932) for the first time in the spring of 1918, when he thought he needed to undergo brain surgery because he feared he would develop facial paralysis. In 1904, Proust turned to Dr Jules Dejerine (1849–1917), Charcot's second successor at the <em>Clinique des Maladies du Systèmes Nerveux</em> at <em>La Salpétrière</em>.</section></section><section><section><h2>Conclusions</h2>Proust's illnesses influenced his work, so much so that some scholars have suggested that there is a very close correlation between his creative genius and the ailments he suffered from, particularly insomnia and asthma.Proust suffered from asthma throughout his life, but the list of his other symptoms is extensive: neurasthenia, anxiety, palpitations, headaches, stomach upsets, hay fever, insomnia, slurred","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"168 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072380","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":"Dupilumab for chronic obstructive pulmonary disease with type 2 inflammation: a pooled analysis of two phase 3, randomised, double-blind, placebo-controlled trials","authors":"Surya P Bhatt, Klaus F Rabe, Nicola A Hanania, Claus F Vogelmeier, Mona Bafadhel, Stephanie A Christenson, Alberto Papi, Dave Singh, Elizabeth Laws, Paula Dakin, Jennifer Maloney, Xin Lu, Deborah Bauer, Ashish Bansal, Raolat M Abdulai, Lacey B Robinson","doi":"10.1016/s2213-2600(24)00409-0","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00409-0","url":null,"abstract":"<h3>Background</h3>Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, which are key drivers of type 2 inflammation. We aimed to characterise the efficacy and safety of dupilumab in patients with COPD and type 2 inflammation.<h3>Methods</h3>For this pooled analysis, we pooled and analysed data from all patients in the intention-to-treat populations of the phase 3, randomised, double-blind, placebo-controlled BOREAS and NOTUS trials, which comprised 206 hospitals and clinics in BOREAS and 217 in NOTUS in 38 countries across Europe, Asia, North America, South America, Africa, and Australia. Eligible patients were current or former smokers with 10 pack-years or more of smoking history, were aged 40–85 years, had physician-diagnosed COPD for at least 12 months before randomisation, had a post-bronchodilator FEV<sub>1</sub>/forced vital capacity (FVC) ratio of less than 0·7, had a post-bronchodilator percentage predicted FEV<sub>1</sub> of 30–70%, had documented evidence of two moderate or one severe exacerbations of COPD in the previous year (at least one exacerbation had to have occurred on triple therapy), and had blood eosinophil counts 300 cells per μL or more during screening. Patients had to have symptomatic COPD and a reported chronic productive cough for at least 3 months in the previous year. Key exclusion criteria were history of asthma, pulmonary disease other than COPD, or other diagnosed pulmonary or systemic disease associated with elevated blood eosinophil. In both trials, eligible patients were randomly assigned (1:1) via block randomisation with block size 4 to receive subcutaneous dupilumab 300 mg or matching placebo once every 2 weeks for 52 weeks, alongside established background therapy with inhaled corticosteroids, a long-acting β2-agonist, and a long-acting muscarinic antagonist. The primary endpoint was the annualised rate of moderate or severe exacerbations over 52 weeks.<h3>Findings</h3>1874 patients were randomly assigned in BOREAS and NOTUS from May 9, 2019, to May 23, 2023; 938 (50·1%) were randomly assigned to the dupilumab groups and 936 (49·9%) were randomly assigned to the placebo groups. Mean age across both groups was 65·1 years (SD 8·2). 622 (33·2%) of 1874 patients were female and 1252 (66·8%) were male. 1628 (86·9%) patients were White, 719 (38·4%) were from Eastern Europe, and 1316 (70·2%) were former smokers. During the 52-week treatment period, 559 moderate or severe exacerbations were reported in 338 (36·0%) of 938 patients in the dupilumab group and 774 exacerbations were reported in 394 (42·1%) of 936 patients in the placebo group. There was a reduction in the annualised rate of moderate or severe exacerbations compared with placebo (annualised exacerbation rate 0·794 in the dupilumab group and 1·156 in the placebo group; incidence rate ratio 0·687, 95% CI 0·595–0·793; p<0·0001). In the dupilumab group, the time to first severe exacerbation was longer th","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"11 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072381","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":"Corticosteroids in community-acquired pneumonia: a step forward, but questions remain","authors":"Luis Felipe Reyes, Ignacio Martin-Loeches","doi":"10.1016/s2213-2600(24)00418-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00418-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"60 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056980","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":"Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials","authors":"Jim M Smit, Philip A Van Der Zee, Sara C M Stoof, Michel E Van Genderen, Dominic Snijders, Wim G Boersma, Paola Confalonieri, Francesco Salton, Marco Confalonieri, Mei-Chiung Shih, Gianfranco U Meduri, Pierre-François Dequin, Amélie Le Gouge, Melanie Lloyd, Harin Karunajeewa, Grzegorz Bartminski, Silvia Fernández-Serrano, Guillermo Suárez-Cuartín, David van Klaveren, Matthias Briel, Henrik Endeman","doi":"10.1016/s2213-2600(24)00405-3","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00405-3","url":null,"abstract":"<h3>Background</h3>Despite several randomised controlled trials (RCTs) on the use of adjuvant treatment with corticosteroids in patients with community-acquired pneumonia (CAP), the effect of this intervention on mortality remains controversial. We aimed to evaluate heterogeneity of treatment effect (HTE) of adjuvant treatment with corticosteroids on 30-day mortality in patients with CAP.<h3>Methods</h3>In this individual patient data meta-analysis, we included RCTs published before July 1, 2024, comparing adjuvant treatment with corticosteroids versus placebo in patients hospitalised with CAP. The primary endpoint was 30-day all-cause mortality, collected across all trials, and analyses followed the intention-to-treat principle. We analysed HTE using risk and effect modelling. For risk modelling, patients were classified as having less severe or severe CAP based on the pneumonia severity index (PSI), comparing PSI class I–III versus class IV–V. For effect modelling, we trained a corticosteroid-effect model on six trials and externally validated it using data from two trials, received after model preregistration. This model classified patients into two groups: no predicted benefit and predicted benefit from adjuvant treatment with corticosteroids. The literature search was registered on PROSPERO, CRD42022380746.<h3>Findings</h3>We included eight RCTs with 3224 patients. Across all eight trials, 246 (7·6%) patients died within 30 days (106 [6·6%] of 1618 in the corticosteroid group <em>vs</em> 140 [8·7%] of 1606 in the placebo group; odds ratio [OR] 0·72 [95% CI 0·56–0·94], p=0·017). The corticosteroid-effect model, which selected C-reactive protein (CRP), showed significant HTE during external validation in the two most recent trials. In these trials, 154 (11·4%) of 1355 patients died within 30 days (88 [13·1%] of 671 in the placebo group <em>vs</em> 66 [9·6%] of 684 in the corticosteroid group; OR 0·71 [95% CI 0·50–0·99], p=0·044). Among patients predicted to have no benefit (CRP ≤204 mg/L, n=725), no significant effect was observed (OR 0·98 [95% CI 0·63–1·50]), whereas for those with predicted benefit (CRP >204 mg/L, n=630), 39 (13·0%) of 301 patients died in the placebo group compared with 20 (6·1%) of 329 in the corticosteroid group (0·43 [0·25–0·76], p<sub>interaction</sub>=0·026). No significant HTE was found between less severe CAP (PSI class I–III, n=229) and severe CAP (PSI class IV–V, n=1126). Corticosteroid therapy significantly increased hyperglycaemia risk (44 [12·8%] of 344 in the placebo group <em>vs</em> 84 [24·8%] of 339 in the corticosteroid group; OR 2·50 [95% CI 1·63–3·83], p<0·0001) and hospital re-admission risk (30 [3·7%] of 814 in the placebo group <em>vs</em> 57 [7·0%] of 819 in the corticosteroid group; 1·95 [1·24–3·07], p=0·0038).<h3>Interpretation</h3>Overall, adjuvant therapy with corticosteroids significantly reduces 30-day mortality in patients hospitalised with CAP. The treatment effect varied significantly a","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"36 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056979","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":"Wildfires in southern California: concerns for lung health","authors":"Talha Burki","doi":"10.1016/s2213-2600(25)00016-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00016-5","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"203 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050777","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":"Population-based cancer registries: an essential partner in monitoring and establishing critical action points","authors":"Talha Burki","doi":"10.1016/s2213-2600(25)00012-8","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00012-8","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"12 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020362","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":"PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial","authors":"Scott M Norberg, Janet Valdez, Scott Napier, Meg Kenyon, Erin Ferraro, Melissa Wheatley, Laura Parsons-Wandell, Stacey L Doran, Amy Lankford, Helen Sabzevari, Douglas E Brough, Jeffrey Schlom, James L Gulley, Clint T Allen","doi":"10.1016/s2213-2600(24)00368-0","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00368-0","url":null,"abstract":"<h3>Background</h3>Recurrent respiratory papillomatosis (RRP) is a rare debilitating condition caused by chronic infection with human papillomavirus (HPV) type 6 or 11. Papillomas develop in the aerodigestive tract, leading to significant voice disturbance and airway obstruction. No systemic treatment currently exists. We aimed to assess the safety and clinical activity of PRGN-2012 in adult patients with RRP treated at the recommended phase 2 dose.<h3>Methods</h3>This was a single-centre, single-arm, phase 1/2 trial. Adult patients aged 18 years or older with RRP who required three or more interventions in the 1 year before treatment received adjuvant PRGN-2012 on day 1 following surgical debulking of disease, and on days 15, 43, and 85. Primary outcome measure was complete response rate, defined as the percentage of patients who did not require an intervention to control RRP in the 12 months after treatment. Safety outcomes included treatment-related adverse events. This study is registered <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT04724980</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>).<h3>Findings</h3>From March 16, 2021, to June 1, 2023, 38 patients were enrolled and received the 12-week treatment course. Among the 35 patients treated at the recommended phase 2 dose of 5×10¹¹ particle units, 18 (51%) of 35 patients had a complete response (95% CI 34–69) with the median duration of complete response yet to be reached. Adverse events were mild and included grades 1–2 injection site reaction (34 [97%] of 35), fatigue (28 [80%] of 35), chills (25 [71%] of 35), and fever (24 [69%] of 35).<h3>Interpretation</h3>PRGN-2012 treatment resulted in complete response in 51% of the patients treated and was safe. Based on these positive pivotal study results, a biologics license application to the US Food and Drug Administration (FDA) is planned, positioning PRGN-2012 to be an FDA-approved medical treatment for adult patients with RRP.<h3>Funding</h3>National Institutes of Health.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"10 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992103","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}