Baohui Han, Trevor Feinstein, Yuankai Shi, Gongyan Chen, Yu Yao, Chunhong Hu, Jianhua Shi, Jifeng Feng, Huijuan Wu, Ying Cheng, Qi-Sen Guo, Zhijun Jie, Feng Ye, Yiping Zhang, Zhihua Liu, Weidong Mao, Liangming Zhang, Junguo Lu, Jun Zhao, Lyudmila Bazhenova, Jimmy Ruiz, Goetz H Kloecker, Kalmadi R Sujith, Ira A Oliff, Matthew Wong, Bin Liu, Yanping Wu, Lan Huang, Yan Sun
{"title":"普利那布林加多西他赛与多西他赛治疗铂类药物治疗疾病进展后的非小细胞肺癌患者（DUBLIN-3）：国际多中心、单盲、平行分组、随机对照试验 3 期。","authors":"Baohui Han, Trevor Feinstein, Yuankai Shi, Gongyan Chen, Yu Yao, Chunhong Hu, Jianhua Shi, Jifeng Feng, Huijuan Wu, Ying Cheng, Qi-Sen Guo, Zhijun Jie, Feng Ye, Yiping Zhang, Zhihua Liu, Weidong Mao, Liangming Zhang, Junguo Lu, Jun Zhao, Lyudmila Bazhenova, Jimmy Ruiz, Goetz H Kloecker, Kalmadi R Sujith, Ira A Oliff, Matthew Wong, Bin Liu, Yanping Wu, Lan Huang, Yan Sun","doi":"10.1016/S2213-2600(24)00178-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>There is an unmet need for second-line and third-line treatments that are effective and tolerable for advanced or metastatic non-small-cell lung cancer (NSCLC) with no driver mutations.</p><p><strong>Methods: </strong>In this phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial, we enrolled patients from 58 medical centres in Australia, China, and the USA. Eligible patients were adults with epidermal growth factor receptor (EGFR) wild-type NSCLC who had progressed after first-line platinum-based therapy. Patients were randomly assigned (1:1) using an independent stratified randomisation schedule with a block size of four to receive intravenous docetaxel 75 mg/m<sup>2</sup> on day 1 and either plinabulin (30 mg/m<sup>2</sup>) or placebo on days 1 and 8 in 21-day cycles until progression, unacceptable toxic effects, withdrawal, or death. The primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Safety was analysed in all patients who had received at least one dose of study drug or placebo. This trial is registered with ClinicalTrials.gov (NCT02504489) and is now closed.</p><p><strong>Findings: </strong>Between Nov 30, 2015, and Jan 6, 2021, 919 patients were screened for inclusion. 360 patients were excluded, and 559 were enrolled and randomly assigned to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). 406 (73%) of 559 patients were male, 153 (27%) were female, and 488 (87%) were Asian. Median OS was 10·5 months (95% CI 9·34-11·87) in the plinabulin group compared with 9·4 months (8·38-10·68) in the control group (stratified HR 0·82, 95% CI 0·68-0·99; p=0·0399). Mean OS was 15·08 months (13·42-16·74) in the plinabulin group compared with 12·77 months (11·45-14·10) in the placebo group using restricted mean survival time analysis (difference 2·31 months, 95% CI 0·18-4·44; p=0·0332). Treatment-emergent adverse events occurred in 273 (>99%) of 274 patients in the plinabulin group and 276 (99%) of 278 patients in the control group. Grade 3 or 4 gastrointestinal disorders occurred more frequently in the plinabulin group than in the placebo group, with the most frequent being diarrhoea (24 [9%] of 274 patients vs three [1%] of 278) and vomiting (six [2%] vs one [<1%]), as did transient grade 3 hypertension (50 [18%] vs eight [3%]). Treatment-emergent death was reported in 12 patients (4%) in the plinabulin group and ten patients (4%) in the placebo group.</p><p><strong>Interpretation: </strong>Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population.</p><p><strong>Funding: </strong>BeyondSpring Pharmaceuticals.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"775-786"},"PeriodicalIF":38.7000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial.\",\"authors\":\"Baohui Han, Trevor Feinstein, Yuankai Shi, Gongyan Chen, Yu Yao, Chunhong Hu, Jianhua Shi, Jifeng Feng, Huijuan Wu, Ying Cheng, Qi-Sen Guo, Zhijun Jie, Feng Ye, Yiping Zhang, Zhihua Liu, Weidong Mao, Liangming Zhang, Junguo Lu, Jun Zhao, Lyudmila Bazhenova, Jimmy Ruiz, Goetz H Kloecker, Kalmadi R Sujith, Ira A Oliff, Matthew Wong, Bin Liu, Yanping Wu, Lan Huang, Yan Sun\",\"doi\":\"10.1016/S2213-2600(24)00178-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>There is an unmet need for second-line and third-line treatments that are effective and tolerable for advanced or metastatic non-small-cell lung cancer (NSCLC) with no driver mutations.</p><p><strong>Methods: </strong>In this phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial, we enrolled patients from 58 medical centres in Australia, China, and the USA. Eligible patients were adults with epidermal growth factor receptor (EGFR) wild-type NSCLC who had progressed after first-line platinum-based therapy. Patients were randomly assigned (1:1) using an independent stratified randomisation schedule with a block size of four to receive intravenous docetaxel 75 mg/m<sup>2</sup> on day 1 and either plinabulin (30 mg/m<sup>2</sup>) or placebo on days 1 and 8 in 21-day cycles until progression, unacceptable toxic effects, withdrawal, or death. The primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Safety was analysed in all patients who had received at least one dose of study drug or placebo. This trial is registered with ClinicalTrials.gov (NCT02504489) and is now closed.</p><p><strong>Findings: </strong>Between Nov 30, 2015, and Jan 6, 2021, 919 patients were screened for inclusion. 360 patients were excluded, and 559 were enrolled and randomly assigned to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). 406 (73%) of 559 patients were male, 153 (27%) were female, and 488 (87%) were Asian. Median OS was 10·5 months (95% CI 9·34-11·87) in the plinabulin group compared with 9·4 months (8·38-10·68) in the control group (stratified HR 0·82, 95% CI 0·68-0·99; p=0·0399). Mean OS was 15·08 months (13·42-16·74) in the plinabulin group compared with 12·77 months (11·45-14·10) in the placebo group using restricted mean survival time analysis (difference 2·31 months, 95% CI 0·18-4·44; p=0·0332). Treatment-emergent adverse events occurred in 273 (>99%) of 274 patients in the plinabulin group and 276 (99%) of 278 patients in the control group. Grade 3 or 4 gastrointestinal disorders occurred more frequently in the plinabulin group than in the placebo group, with the most frequent being diarrhoea (24 [9%] of 274 patients vs three [1%] of 278) and vomiting (six [2%] vs one [<1%]), as did transient grade 3 hypertension (50 [18%] vs eight [3%]). Treatment-emergent death was reported in 12 patients (4%) in the plinabulin group and ten patients (4%) in the placebo group.</p><p><strong>Interpretation: </strong>Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population.</p><p><strong>Funding: </strong>BeyondSpring Pharmaceuticals.</p>\",\"PeriodicalId\":51307,\"journal\":{\"name\":\"Lancet Respiratory Medicine\",\"volume\":\" \",\"pages\":\"775-786\"},\"PeriodicalIF\":38.7000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lancet Respiratory Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/S2213-2600(24)00178-4\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lancet Respiratory Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/S2213-2600(24)00178-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial.
Background: There is an unmet need for second-line and third-line treatments that are effective and tolerable for advanced or metastatic non-small-cell lung cancer (NSCLC) with no driver mutations.
Methods: In this phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial, we enrolled patients from 58 medical centres in Australia, China, and the USA. Eligible patients were adults with epidermal growth factor receptor (EGFR) wild-type NSCLC who had progressed after first-line platinum-based therapy. Patients were randomly assigned (1:1) using an independent stratified randomisation schedule with a block size of four to receive intravenous docetaxel 75 mg/m2 on day 1 and either plinabulin (30 mg/m2) or placebo on days 1 and 8 in 21-day cycles until progression, unacceptable toxic effects, withdrawal, or death. The primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Safety was analysed in all patients who had received at least one dose of study drug or placebo. This trial is registered with ClinicalTrials.gov (NCT02504489) and is now closed.
Findings: Between Nov 30, 2015, and Jan 6, 2021, 919 patients were screened for inclusion. 360 patients were excluded, and 559 were enrolled and randomly assigned to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). 406 (73%) of 559 patients were male, 153 (27%) were female, and 488 (87%) were Asian. Median OS was 10·5 months (95% CI 9·34-11·87) in the plinabulin group compared with 9·4 months (8·38-10·68) in the control group (stratified HR 0·82, 95% CI 0·68-0·99; p=0·0399). Mean OS was 15·08 months (13·42-16·74) in the plinabulin group compared with 12·77 months (11·45-14·10) in the placebo group using restricted mean survival time analysis (difference 2·31 months, 95% CI 0·18-4·44; p=0·0332). Treatment-emergent adverse events occurred in 273 (>99%) of 274 patients in the plinabulin group and 276 (99%) of 278 patients in the control group. Grade 3 or 4 gastrointestinal disorders occurred more frequently in the plinabulin group than in the placebo group, with the most frequent being diarrhoea (24 [9%] of 274 patients vs three [1%] of 278) and vomiting (six [2%] vs one [<1%]), as did transient grade 3 hypertension (50 [18%] vs eight [3%]). Treatment-emergent death was reported in 12 patients (4%) in the plinabulin group and ten patients (4%) in the placebo group.
Interpretation: Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population.
期刊介绍：
The Lancet Respiratory Medicine is a renowned journal specializing in respiratory medicine and critical care. Our publication features original research that aims to advocate for change or shed light on clinical practices in the field. Additionally, we provide informative reviews on various topics related to respiratory medicine and critical care, ensuring a comprehensive coverage of the subject.
The journal covers a wide range of topics including but not limited to asthma, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), tobacco control, intensive care medicine, lung cancer, cystic fibrosis, pneumonia, sarcoidosis, sepsis, mesothelioma, sleep medicine, thoracic and reconstructive surgery, tuberculosis, palliative medicine, influenza, pulmonary hypertension, pulmonary vascular disease, and respiratory infections. By encompassing such a broad spectrum of subjects, we strive to address the diverse needs and interests of our readership.
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