{"title":"Health promotion in the management of respiratory diseases: an Indian perspective","authors":"Arundhati Garud, Debabani Biswas, Saibal Moitra, Subhabrata Moitra","doi":"10.1016/s2213-2600(24)00332-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00332-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"60 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542070","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}
<h3>Background</h3>Combined treatment with anti-PD-1 and anti-CTLA-4 antibodies has shown superiority over chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC), but data for older patients (aged ≥70 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 or those with an ECOG performance status of 2 are scarce. We aimed to test the superiority of the PD-1 antibody nivolumab and the CTLA-4 antibody ipilimumab over platinum-based doublet chemotherapy as first-line treatment in patients with NSCLC aged 70 years or older or with an ECOG performance status of 2.<h3>Methods</h3>This open-label, multicentre, randomised, controlled, phase 3 trial was done at 30 hospitals and cancer centres in France. Eligible patients had stage IV histologically proven NSCLC, with no known oncogenic alterations, and were either aged 70 years or older with ECOG performance status of 0–2 or younger than 70 years with an ECOG performance status of 2. Patients were randomly assigned (1:1) centrally, using a computer-generated algorithm stratified by age (<70 <em>vs</em> ≥70 years), ECOG performance status (0–1 <em>vs</em> 2), and histology (squamous <em>vs</em> non-squamous) to receive nivolumab plus ipilimumab or platinum-based doublet chemotherapy (carboplatin [area under the curve ≤700 mg] plus pemetrexed [500 mg/m<sup>2</sup> intravenous infusion every 3 weeks] or carboplatin [on day 1; area under the curve ≤700 mg] plus paclitaxel [90 mg/m<sup>2</sup> as intravenous infusion on days 1, 5, and 15, every 4 weeks]). The primary endpoint was overall survival; secondary endpoints included progression-free survival and safety. All efficacy analyses were performed in the intention-to-treat population, which included all randomly assigned patients. Safety was analysed in the safety analysis set, which included all randomly assigned patients who received at least one dose of study treatment and who had at least one safety follow-up. The 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>NCT03351361</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>The trial was stopped early for futility on the basis of a pre-planned interim analysis after 33% of the expected events had occurred. Between Feb 12, 2018, and Dec 15, 2020, 217 patients were randomly assigned, of whom 216 patients were included in the final analysis, with 109 patients in the nivolumab plus ipilimumab group and 107 in the chemotherapy group; median age was 74 years (IQR 70–78). Median overall survival was 14·7 months (95% CI 8·0–19·7) in the nivolumab plus ipilimumab
背景在晚期非小细胞肺癌（NSCLC）患者中，抗PD-1抗体和抗CTLA-4抗体的联合治疗已显示出优于化疗的效果，但针对东部合作肿瘤学组（ECOG）表现为0-1级或ECOG表现为2级的老年患者（年龄≥70岁）的数据却很少。我们的目的是检验 PD-1 抗体 nivolumab 和 CTLA-4 抗体 ipilimumab 作为 70 岁或以上或 ECOG 表现为 2 的 NSCLC 患者一线治疗的疗效是否优于铂类双联化疗。方法这项开放标签、多中心、随机对照的 3 期试验在法国的 30 家医院和癌症中心进行。符合条件的患者均为组织学证实的 NSCLC IV 期患者，无已知致癌基因改变，年龄在 70 岁或以上且 ECOG 表现为 0-2 级，或年龄在 70 岁以下且 ECOG 表现为 2 级。患者随机分配（1：1），采用计算机生成的算法，按年龄（70 岁 vs ≥70 岁）、ECOG 表现状态（0-1 vs 2）和组织学（鳞状 vs 非鳞状）分层，接受 nivolumab 加 ipilimumab 或铂类双联化疗（卡铂[曲线下面积≤700 毫克]加培美曲塞[每 3 周 500 毫克/平方米静脉注射]或卡铂[第 1 天；曲线下面积≤700 毫克]加紫杉醇[90 毫克/平方米，静脉注射，第 1、5 和 15 天，每 4 周一次]）。主要终点是总生存期，次要终点包括无进展生存期和安全性。所有疗效分析均在意向治疗人群中进行，包括所有随机分配的患者。安全性分析在安全性分析组中进行，该分析组包括所有随机分配的患者，他们至少接受了一个剂量的研究治疗，并且至少进行了一次安全性随访。该试验已在ClinicalTrials.gov注册，编号为NCT03351361.研究结果在33%的预期事件发生后，根据预先计划的中期分析，该试验因无效而提前终止。2018年2月12日至2020年12月15日期间，217名患者被随机分配，其中216名患者纳入最终分析，nivolumab加伊匹单抗组109人，化疗组107人；中位年龄为74岁（IQR 70-78）。nivolumab加伊匹单抗组的中位总生存期为14-7个月（95% CI 8-0-19-7），化疗组为9-9个月（7-7-12-3）（危险比[HR] 0-85 [95% CI 0-62-1-16]）。在70岁或以上、ECOG表现为0-1的患者中（中位年龄76岁[IQR 73-79]），nivolumab联合伊匹单抗组的中位总生存期长于化疗组：分别为22-6个月（95% CI 18-1-36-0）和11-8个月（8-9-20-5；HR 0-64 [95% CI 0-46-0-96]）。在ECOG表现为2级（中位年龄69岁[IQR 63-75]）的患者中，nivolumab加伊匹单抗组的中位总生存期为2-9个月（95% CI 1-4-4-8），而化疗组为6-1个月（3-5-10-4）（HR 1-32 [95% CI 0-82-2-11]）。未报告新的安全性信号。最常见的3级或更严重不良事件是化疗组的中性粒细胞减少（103例患者中有28例[27%]），以及nivolumab加伊匹单抗组的内分泌紊乱（105例患者中有5例[5%]）、心脏紊乱（10例[10%]）和胃肠道紊乱（11例[11%]）。由于提前停药，该试验的主要和次要终点指标不足；然而，在ECOG表现状态为0-1的老年NSCLC患者亚组中，与铂类双药相比，nivolumab加伊匹单抗的生存率更高，这一发现值得进一步研究。
{"title":"Nivolumab plus ipilimumab versus carboplatin-based doublet as first-line treatment for patients with advanced non-small-cell lung cancer aged ≥70 years or with an ECOG performance status of 2 (GFPC 08–2015 ENERGY): a randomised, open-label, phase 3 study","authors":"Hervé Léna, Laurent Greillier, Claire Cropet, Olivier Bylicki, Isabelle Monnet, Clarisse Audigier-Valette, Lionel Falchero, Alain Vergnenègre, Pierre Demontrond, Margaux Geier, Florian Guisier, Stéphane Hominal, Chrystèle Locher, Romain Corre, Christos Chouaid, Charles Ricordel","doi":"10.1016/s2213-2600(24)00264-9","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00264-9","url":null,"abstract":"<h3>Background</h3>Combined treatment with anti-PD-1 and anti-CTLA-4 antibodies has shown superiority over chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC), but data for older patients (aged ≥70 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 or those with an ECOG performance status of 2 are scarce. We aimed to test the superiority of the PD-1 antibody nivolumab and the CTLA-4 antibody ipilimumab over platinum-based doublet chemotherapy as first-line treatment in patients with NSCLC aged 70 years or older or with an ECOG performance status of 2.<h3>Methods</h3>This open-label, multicentre, randomised, controlled, phase 3 trial was done at 30 hospitals and cancer centres in France. Eligible patients had stage IV histologically proven NSCLC, with no known oncogenic alterations, and were either aged 70 years or older with ECOG performance status of 0–2 or younger than 70 years with an ECOG performance status of 2. Patients were randomly assigned (1:1) centrally, using a computer-generated algorithm stratified by age (<70 <em>vs</em> ≥70 years), ECOG performance status (0–1 <em>vs</em> 2), and histology (squamous <em>vs</em> non-squamous) to receive nivolumab plus ipilimumab or platinum-based doublet chemotherapy (carboplatin [area under the curve ≤700 mg] plus pemetrexed [500 mg/m<sup>2</sup> intravenous infusion every 3 weeks] or carboplatin [on day 1; area under the curve ≤700 mg] plus paclitaxel [90 mg/m<sup>2</sup> as intravenous infusion on days 1, 5, and 15, every 4 weeks]). The primary endpoint was overall survival; secondary endpoints included progression-free survival and safety. All efficacy analyses were performed in the intention-to-treat population, which included all randomly assigned patients. Safety was analysed in the safety analysis set, which included all randomly assigned patients who received at least one dose of study treatment and who had at least one safety follow-up. The 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>NCT03351361</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>The trial was stopped early for futility on the basis of a pre-planned interim analysis after 33% of the expected events had occurred. Between Feb 12, 2018, and Dec 15, 2020, 217 patients were randomly assigned, of whom 216 patients were included in the final analysis, with 109 patients in the nivolumab plus ipilimumab group and 107 in the chemotherapy group; median age was 74 years (IQR 70–78). Median overall survival was 14·7 months (95% CI 8·0–19·7) in the nivolumab plus ipilimumab","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"62 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541685","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}
Pub Date : 2024-10-29DOI: 10.1016/s2213-2600(24)00306-0
Martin R Miller, Brian L Graham, Sanja Stanojevic
No Abstract
无摘要
{"title":"Spirometry in female individuals","authors":"Martin R Miller, Brian L Graham, Sanja Stanojevic","doi":"10.1016/s2213-2600(24)00306-0","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00306-0","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"238 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541686","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}
Pub Date : 2024-10-29DOI: 10.1016/s2213-2600(24)00326-6
Moll M, Sakornsakolpat P, Shrine N, et al. Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts. Lancet Respir Med 2020; 8: 696–708—In this Article, a subset of participants from the SPIROMICS cohort were included in the study who were later found to have not provided consent for genetics or to have withdrawn consent for genetics. SPIROMICS I enrolled participants from 2010 to 2016 and performed up to three follow-up visits up to 2016. During SPIROMICS I, the consent form included several questions, including one on genetics. At each follow-up visit, the consent form was repeated and blood was drawn. This process yielded a complex set of consent flags and biospecimens across up to four visits. Unfortunately, the consent flags extracted from consent form questions were not properly reviewed before the isolation of DNA from the stored blood. Therefore, in 2016, some participants who did not consent for genetics, or who had withdrawn consent for genetics, had DNA isolated from blood and were included in the genome-wide association study. To correct the use of SPIROMICS data in this Article, the individuals who did not provide or who withdrew consent (11 controls and 15 cases) were removed and all analyses involving SPIROMICS data were repeated. In figure 2, the odds ratio (OR) for the association of combined polygenic risk score with chronic obstructive pulmonary disease (COPD) was corrected to 2·15 (95% CI 1·88–2·46) for the SPIROMICS non-Hispanic white (NHW) cohort, to 1·82 (1·74–1·89) for the overall fixed-effect model for European cohorts, and to 1·84 (1·60–2·11) for the overall random-effects model for European cohorts. In figure 3A, the ORs for COPD in European cohorts were corrected. In figure 4, the areas under the curve for predicting COPD in the SPIROMICS NHW cohort were corrected. The appendix has also been corrected. None of the findings changed significantly, and the conclusions of the study are unaffected. These corrections have been made to the online version as of Oct 29, 2024.
Moll M, Sakornsakolpat P, Shrine N, et al. 慢性阻塞性肺病及相关表型：基于人群和病例对照队列的多基因风险评分。Lancet Respir Med 2020; 8: 696-708-在这篇文章中，SPIROMICS队列中的一部分参与者被纳入了研究，但后来发现他们没有提供遗传学同意书或撤回了遗传学同意书。SPIROMICS I在2010年至2016年期间招募了参与者，并在2016年之前进行了最多三次随访。在 SPIROMICS I 期间，同意书包括几个问题，其中一个是关于遗传学的问题。每次随访时，都要重复填写同意书并抽血。这一过程产生了一组复杂的同意标记和生物样本，涉及多达四次就诊。遗憾的是，在从储存的血液中分离 DNA 之前，没有对从同意书问题中提取的同意标志进行适当审查。因此，2016 年，一些未同意遗传学研究或已撤销遗传学研究同意的参与者从血液中分离出了 DNA，并被纳入了全基因组关联研究。为了纠正本文对 SPIROMICS 数据的使用，删除了未提供同意书或撤回同意书的个体（11 例对照和 15 例病例），并重复了所有涉及 SPIROMICS 数据的分析。在图2中，SPIROMICS非西班牙裔白人（NHW）队列的综合多基因风险评分与慢性阻塞性肺病（COPD）相关性的比值比（OR）被校正为2-15（95% CI 1-88-2-46），欧洲队列的总体固定效应模型的比值比（OR）被校正为1-82（1-74-1-89），欧洲队列的总体随机效应模型的比值比（OR）被校正为1-84（1-60-2-11）。在图 3A 中，对欧洲队列中慢性阻塞性肺病的 ORs 进行了校正。在图 4 中，对 SPIROMICS NHW 队列中预测慢性阻塞性肺病的曲线下面积进行了更正。附录也做了更正。所有结果均无重大变化，研究结论不受影响。这些更正已在 2024 年 10 月 29 日的在线版本中做出。
{"title":"Correction to Lancet Respir Med 2020; 8: 696–708","authors":"","doi":"10.1016/s2213-2600(24)00326-6","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00326-6","url":null,"abstract":"<em>Moll M, Sakornsakolpat P, Shrine N, et al. Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts.</em> Lancet Respir Med <em>2020; <strong>8:</strong> 696–708</em>—In this Article, a subset of participants from the SPIROMICS cohort were included in the study who were later found to have not provided consent for genetics or to have withdrawn consent for genetics. SPIROMICS I enrolled participants from 2010 to 2016 and performed up to three follow-up visits up to 2016. During SPIROMICS I, the consent form included several questions, including one on genetics. At each follow-up visit, the consent form was repeated and blood was drawn. This process yielded a complex set of consent flags and biospecimens across up to four visits. Unfortunately, the consent flags extracted from consent form questions were not properly reviewed before the isolation of DNA from the stored blood. Therefore, in 2016, some participants who did not consent for genetics, or who had withdrawn consent for genetics, had DNA isolated from blood and were included in the genome-wide association study. To correct the use of SPIROMICS data in this Article, the individuals who did not provide or who withdrew consent (11 controls and 15 cases) were removed and all analyses involving SPIROMICS data were repeated. In figure 2, the odds ratio (OR) for the association of combined polygenic risk score with chronic obstructive pulmonary disease (COPD) was corrected to 2·15 (95% CI 1·88–2·46) for the SPIROMICS non-Hispanic white (NHW) cohort, to 1·82 (1·74–1·89) for the overall fixed-effect model for European cohorts, and to 1·84 (1·60–2·11) for the overall random-effects model for European cohorts. In figure 3A, the ORs for COPD in European cohorts were corrected. In figure 4, the areas under the curve for predicting COPD in the SPIROMICS NHW cohort were corrected. The appendix has also been corrected. None of the findings changed significantly, and the conclusions of the study are unaffected. These corrections have been made to the online version as of Oct 29, 2024.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"130 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541689","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}
Pub Date : 2024-10-29DOI: 10.1016/s2213-2600(24)00365-5
Ziming Li, Shun Lu
No Abstract
无摘要
{"title":"First-line treatment for advanced NSCLC in older patients and those with poor performance status","authors":"Ziming Li, Shun Lu","doi":"10.1016/s2213-2600(24)00365-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00365-5","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"86 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541684","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}
Pub Date : 2024-10-25DOI: 10.1016/s2213-2600(24)00217-0
Sergio Harari, Davide Elia, Antonella Caminati, Jens Geginat, Francesca Luisi, Giuseppe Pelosi, Claudia Specchia, Olga Torre, Roberta Trevisan, Chiara Vasco, Maurizio Zompatori, Roberto Cassandro
<h3>Background</h3>Lymphangioleiomyomatosis is an ultra-rare disease mainly affecting women of childbearing age. The MILES trial showed the efficacy of sirolimus, an mTOR inhibitor, in stabilising lung function in patients with lymphangioleiomyomatosis. Drug toxicity and development of resistance are potential limitations of therapy with sirolimus. Nintedanib is a multikinase inhibitor that inhibits PDGFR, which is active in human and murine lymphangioleiomyomatosis lesions. We aimed to investigate the activity and safety of nintedanib in patients with lymphangioleiomyomatosis.<h3>Methods</h3>This phase 2, open-label, single-arm study was conducted at MultiMedica IRCCS, a national referral university centre for rare pulmonary diseases in Milan, Italy. Eligible participants were aged 18 years and older and had sporadic or tuberous sclerosis complex-associated lymphangioleiomyomatosis with progressive pulmonary function decline in the past year despite treatment with sirolimus or treatment naive. Patients received nintedanib 150 mg orally twice per day, with a possible reduction to 100 mg twice per day in case of side-effects or hepatoxicity, for 12 months, followed by a period of 12 additional months without study treatment. The primary endpoint was the change in FEV<sub>1</sub> (FEV<sub>1</sub> slope in L) over 12 months. This study 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>NCT03062943</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 Oct 14, 2016, to Dec 13, 2019, 35 female patients (mean age 50 years [SD 11]) entered the study, 30 of whom were eligible and received nintedanib. After 12 months, 22 patients completed the treatment, 19 of whom also completed the 12 months of follow-up. FEV<sub>1</sub> remained stable after one year of treatment (predicted mean difference 0·001 L [95% CI –0·063 to 0·066]; p=0·97). During the 12 months off treatment, a slight decline in FEV<sub>1</sub> was observed (predicted mean difference –0·076 L [95% CI –0·149 to –0·004]; p=0·040). The most frequent adverse events were nausea (15 [50%] patients), diarrhoea (eight [26%]), and abdominal pain (two [7%]). No serious adverse events were observed during the treatment period.<h3>Interpretation</h3>Our findings suggest that nintedanib did not improve FEV<sub>1</sub>, but that the treatment was generally well tolerated. These results might support nintedanib as a second-line therapy in patients not controlled by standard treatment with mTOR inhibitors. Further investigation, such as a non-inferiority trial comparing nintedanib and sirolimus could help to better
{"title":"Nintedanib for patients with lymphangioleiomyomatosis: a phase 2, open-label, single-arm study","authors":"Sergio Harari, Davide Elia, Antonella Caminati, Jens Geginat, Francesca Luisi, Giuseppe Pelosi, Claudia Specchia, Olga Torre, Roberta Trevisan, Chiara Vasco, Maurizio Zompatori, Roberto Cassandro","doi":"10.1016/s2213-2600(24)00217-0","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00217-0","url":null,"abstract":"<h3>Background</h3>Lymphangioleiomyomatosis is an ultra-rare disease mainly affecting women of childbearing age. The MILES trial showed the efficacy of sirolimus, an mTOR inhibitor, in stabilising lung function in patients with lymphangioleiomyomatosis. Drug toxicity and development of resistance are potential limitations of therapy with sirolimus. Nintedanib is a multikinase inhibitor that inhibits PDGFR, which is active in human and murine lymphangioleiomyomatosis lesions. We aimed to investigate the activity and safety of nintedanib in patients with lymphangioleiomyomatosis.<h3>Methods</h3>This phase 2, open-label, single-arm study was conducted at MultiMedica IRCCS, a national referral university centre for rare pulmonary diseases in Milan, Italy. Eligible participants were aged 18 years and older and had sporadic or tuberous sclerosis complex-associated lymphangioleiomyomatosis with progressive pulmonary function decline in the past year despite treatment with sirolimus or treatment naive. Patients received nintedanib 150 mg orally twice per day, with a possible reduction to 100 mg twice per day in case of side-effects or hepatoxicity, for 12 months, followed by a period of 12 additional months without study treatment. The primary endpoint was the change in FEV<sub>1</sub> (FEV<sub>1</sub> slope in L) over 12 months. This study 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>NCT03062943</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 Oct 14, 2016, to Dec 13, 2019, 35 female patients (mean age 50 years [SD 11]) entered the study, 30 of whom were eligible and received nintedanib. After 12 months, 22 patients completed the treatment, 19 of whom also completed the 12 months of follow-up. FEV<sub>1</sub> remained stable after one year of treatment (predicted mean difference 0·001 L [95% CI –0·063 to 0·066]; p=0·97). During the 12 months off treatment, a slight decline in FEV<sub>1</sub> was observed (predicted mean difference –0·076 L [95% CI –0·149 to –0·004]; p=0·040). The most frequent adverse events were nausea (15 [50%] patients), diarrhoea (eight [26%]), and abdominal pain (two [7%]). No serious adverse events were observed during the treatment period.<h3>Interpretation</h3>Our findings suggest that nintedanib did not improve FEV<sub>1</sub>, but that the treatment was generally well tolerated. These results might support nintedanib as a second-line therapy in patients not controlled by standard treatment with mTOR inhibitors. Further investigation, such as a non-inferiority trial comparing nintedanib and sirolimus could help to better","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"32 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490068","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}
Pub Date : 2024-10-25DOI: 10.1016/s2213-2600(24)00328-x
Maria Molina-Molina
No Abstract
无摘要
{"title":"The challenge of therapeutic options for patients with lymphangioleiomyomatosis","authors":"Maria Molina-Molina","doi":"10.1016/s2213-2600(24)00328-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00328-x","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"60 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490045","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}
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