Christine Auberle, Feng Gao, Mark Sloan, Daniel Morgensztern, Linda Winkler, Jeffrey P Ward, Siddhartha Devarakonda, Timothy P Rearden, Ramaswamy Govindan, Saiama N Waqar
{"title":"尼替达尼在分子筛选出的晚期非小细胞肺癌患者中的试点研究。","authors":"Christine Auberle, Feng Gao, Mark Sloan, Daniel Morgensztern, Linda Winkler, Jeffrey P Ward, Siddhartha Devarakonda, Timothy P Rearden, Ramaswamy Govindan, Saiama N Waqar","doi":"10.21037/jtd-23-1717","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in <i>TP53</i>, <i>VEGFR1-3</i>, <i>PDGFR-A</i>, <i>PDGFR-B</i>, and <i>FGFR1-3</i> treated with nintedanib as part of an open-label, single-arm pilot study.</p><p><strong>Methods: </strong>Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. This study was registered with ClinicalTrials.gov, number NCT02299141.</p><p><strong>Results: </strong>Between 2015 and 2019, 20 patients were enrolled with a median age was 66 years, 15 (75%) were females, 15 (75%) had adenocarcinoma, and 17 patients had a <i>TP53</i> mutation (85%). Seventeen (85%) had received prior immunotherapy and 11 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with three partial responses (PR), while 12 patients had stable disease (SD), with disease control rate (DCR) consisting of a PR and SD greater than or equal to 16 weeks of 65% (n=13). Median PFS was 4.3 months [95% confidence interval (CI): 1.8-7.9] and median overall survival (OS) was 11.3 months (95% CI: 3.5-44.2). Three patients experienced prolonged clinical benefit from nintedanib, remaining on treatment for over 1 year and all three had a <i>TP53</i> mutation and received prior immunotherapy. The most common adverse events of any grade included nausea (80%), fatigue (70%), diarrhea (60%), and anorexia (60%).</p><p><strong>Conclusions: </strong>In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228753/pdf/","citationCount":"0","resultStr":"{\"title\":\"A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer.\",\"authors\":\"Christine Auberle, Feng Gao, Mark Sloan, Daniel Morgensztern, Linda Winkler, Jeffrey P Ward, Siddhartha Devarakonda, Timothy P Rearden, Ramaswamy Govindan, Saiama N Waqar\",\"doi\":\"10.21037/jtd-23-1717\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in <i>TP53</i>, <i>VEGFR1-3</i>, <i>PDGFR-A</i>, <i>PDGFR-B</i>, and <i>FGFR1-3</i> treated with nintedanib as part of an open-label, single-arm pilot study.</p><p><strong>Methods: </strong>Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. This study was registered with ClinicalTrials.gov, number NCT02299141.</p><p><strong>Results: </strong>Between 2015 and 2019, 20 patients were enrolled with a median age was 66 years, 15 (75%) were females, 15 (75%) had adenocarcinoma, and 17 patients had a <i>TP53</i> mutation (85%). Seventeen (85%) had received prior immunotherapy and 11 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with three partial responses (PR), while 12 patients had stable disease (SD), with disease control rate (DCR) consisting of a PR and SD greater than or equal to 16 weeks of 65% (n=13). Median PFS was 4.3 months [95% confidence interval (CI): 1.8-7.9] and median overall survival (OS) was 11.3 months (95% CI: 3.5-44.2). Three patients experienced prolonged clinical benefit from nintedanib, remaining on treatment for over 1 year and all three had a <i>TP53</i> mutation and received prior immunotherapy. The most common adverse events of any grade included nausea (80%), fatigue (70%), diarrhea (60%), and anorexia (60%).</p><p><strong>Conclusions: </strong>In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity.</p>\",\"PeriodicalId\":17542,\"journal\":{\"name\":\"Journal of thoracic disease\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-06-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228753/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of thoracic disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/jtd-23-1717\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of thoracic disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/jtd-23-1717","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/12 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer.
Background: Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in TP53, VEGFR1-3, PDGFR-A, PDGFR-B, and FGFR1-3 treated with nintedanib as part of an open-label, single-arm pilot study.
Methods: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. This study was registered with ClinicalTrials.gov, number NCT02299141.
Results: Between 2015 and 2019, 20 patients were enrolled with a median age was 66 years, 15 (75%) were females, 15 (75%) had adenocarcinoma, and 17 patients had a TP53 mutation (85%). Seventeen (85%) had received prior immunotherapy and 11 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with three partial responses (PR), while 12 patients had stable disease (SD), with disease control rate (DCR) consisting of a PR and SD greater than or equal to 16 weeks of 65% (n=13). Median PFS was 4.3 months [95% confidence interval (CI): 1.8-7.9] and median overall survival (OS) was 11.3 months (95% CI: 3.5-44.2). Three patients experienced prolonged clinical benefit from nintedanib, remaining on treatment for over 1 year and all three had a TP53 mutation and received prior immunotherapy. The most common adverse events of any grade included nausea (80%), fatigue (70%), diarrhea (60%), and anorexia (60%).
Conclusions: In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity.
期刊介绍:
The Journal of Thoracic Disease (JTD, J Thorac Dis, pISSN: 2072-1439; eISSN: 2077-6624) was founded in Dec 2009, and indexed in PubMed in Dec 2011 and Science Citation Index SCI in Feb 2013. It is published quarterly (Dec 2009- Dec 2011), bimonthly (Jan 2012 - Dec 2013), monthly (Jan. 2014-) and openly distributed worldwide. JTD received its impact factor of 2.365 for the year 2016. JTD publishes manuscripts that describe new findings and provide current, practical information on the diagnosis and treatment of conditions related to thoracic disease. All the submission and reviewing are conducted electronically so that rapid review is assured.