{"title":"获批的分子肿瘤学新药（联合或单一疗法）的特点和疗效","authors":"Sruthi Ranganathan , Alyson Haslam , Jordan Tuia , Vinay Prasad","doi":"10.1016/j.jcpo.2023.100462","DOIUrl":null,"url":null,"abstract":"<div><h3>Importance</h3><p>Understanding the factors that are associated with new molecular entity (NME) cancer drug<span> approvals as a single agent and in combination, and European Society for Medical Oncology (ESMO) scores, can aid in identifying suitable factors to consider in trial designs for future drugs. In addition, the association between the various outcomes can aid in determining benefit when surrogate outcomes are used in approval consideration.</span></p></div><div><h3>Objective</h3><p><span>This study aims to (1) use the measures used in evaluating clinical trials<span> by ESMO scores to determine the differences in the characteristics of 2013–2022 Food and Drug Administration (FDA) oncology NME drug approvals for those approved for use in combination or as a </span></span>monotherapy, and (2) analyze the association between survival outcomes and the response rate for monotherapy NME drugs and/or drugs approved in combination.</p></div><div><h3>Design</h3><p>Cross-sectional analysis.</p></div><div><h3>Setting</h3><p>US FDA Oncology Drug Approvals (2013–2022)</p></div><div><h3>Participants</h3><p>US FDA Oncology Drug Approvals (2013–2022)</p></div><div><h3>Exposures</h3><p>Trial-level characteristics (tumor types, basis of approval, randomized or not, phase) and associations between overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) and whether NME drugs were approved as monotherapy or in combination .</p></div><div><h3>Results</h3><p>Drugs approved for use as a monotherapy are less likely to be approved using a randomized study (p < 0.001) and more likely to be approved via the accelerated pathway (p = 0.012) and be open-label (p < 0.001). Drugs approved for use as a combination or monotherapy significantly differed on their approval basis (p = 0.002), phase of trial at the time of approval (p = 0.02), and ESMO scores (p = 0.02). There was low correlation between response rate and either PFS or OS metrics. However, nearly all of the drugs with large improvements in OS (> 5months) were drugs with robust ORR.</p></div><div><h3>Conclusions and relevance</h3><p>Drugs approved as monotherapy with a low response rate are likely to have marginal benefit in OS and PFS.</p></div>","PeriodicalId":38212,"journal":{"name":"Journal of Cancer Policy","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Characteristics and outcomes of new molecular oncology drug approvals, in combination or monotherapy\",\"authors\":\"Sruthi Ranganathan , Alyson Haslam , Jordan Tuia , Vinay Prasad\",\"doi\":\"10.1016/j.jcpo.2023.100462\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Importance</h3><p>Understanding the factors that are associated with new molecular entity (NME) cancer drug<span> approvals as a single agent and in combination, and European Society for Medical Oncology (ESMO) scores, can aid in identifying suitable factors to consider in trial designs for future drugs. In addition, the association between the various outcomes can aid in determining benefit when surrogate outcomes are used in approval consideration.</span></p></div><div><h3>Objective</h3><p><span>This study aims to (1) use the measures used in evaluating clinical trials<span> by ESMO scores to determine the differences in the characteristics of 2013–2022 Food and Drug Administration (FDA) oncology NME drug approvals for those approved for use in combination or as a </span></span>monotherapy, and (2) analyze the association between survival outcomes and the response rate for monotherapy NME drugs and/or drugs approved in combination.</p></div><div><h3>Design</h3><p>Cross-sectional analysis.</p></div><div><h3>Setting</h3><p>US FDA Oncology Drug Approvals (2013–2022)</p></div><div><h3>Participants</h3><p>US FDA Oncology Drug Approvals (2013–2022)</p></div><div><h3>Exposures</h3><p>Trial-level characteristics (tumor types, basis of approval, randomized or not, phase) and associations between overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) and whether NME drugs were approved as monotherapy or in combination .</p></div><div><h3>Results</h3><p>Drugs approved for use as a monotherapy are less likely to be approved using a randomized study (p < 0.001) and more likely to be approved via the accelerated pathway (p = 0.012) and be open-label (p < 0.001). Drugs approved for use as a combination or monotherapy significantly differed on their approval basis (p = 0.002), phase of trial at the time of approval (p = 0.02), and ESMO scores (p = 0.02). There was low correlation between response rate and either PFS or OS metrics. However, nearly all of the drugs with large improvements in OS (> 5months) were drugs with robust ORR.</p></div><div><h3>Conclusions and relevance</h3><p>Drugs approved as monotherapy with a low response rate are likely to have marginal benefit in OS and PFS.</p></div>\",\"PeriodicalId\":38212,\"journal\":{\"name\":\"Journal of Cancer Policy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2023-12-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cancer Policy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213538323000796\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEALTH POLICY & SERVICES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cancer Policy","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213538323000796","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEALTH POLICY & SERVICES","Score":null,"Total":0}
引用次数: 0
摘要
重要性了解与新分子实体(NME)癌症药物单药和联合批准相关的因素，以及欧洲肿瘤医学学会(ESMO)评分，可以帮助确定未来药物试验设计中考虑的合适因素。此外，当替代结果用于批准考虑时，各种结果之间的关联可以帮助确定获益。本研究旨在(1)利用ESMO评分评估临床试验的方法，确定2013-2022年FDA (Food and Drug Administration, FDA)批准的肿瘤NME药物在联合或单一治疗方面的特点差异;(2)分析单一治疗NME药物和/或联合批准的NME药物的生存结局与缓解率之间的关联。DesignCross-sectional分析。美国FDA肿瘤药物批准(2013-2022):暴露水平的特征(肿瘤类型、批准基础、随机与否、分期)和总生存期(OS)、无进展生存期(PFS)或总缓解率(ORR)之间的关系，以及NME药物是被批准作为单一疗法还是联合疗法。结果批准用作单一疗法的药物在随机研究中被批准的可能性较小(p <0.001)，更有可能通过加速途径获得批准(p = 0.012)和开放标签(p <0.001)。被批准作为联合或单一疗法使用的药物在其批准基础(p = 0.002)、批准时的试验阶段(p = 0.02)和ESMO评分(p = 0.02)上存在显著差异。反应率与PFS或OS指标之间的相关性较低。然而，几乎所有对OS有显著改善的药物(>5个月)均为ORR较强的药物。结论和相关性:被批准为单药治疗的低缓解率药物可能在OS和PFS中具有边际效益。
Characteristics and outcomes of new molecular oncology drug approvals, in combination or monotherapy
Importance
Understanding the factors that are associated with new molecular entity (NME) cancer drug approvals as a single agent and in combination, and European Society for Medical Oncology (ESMO) scores, can aid in identifying suitable factors to consider in trial designs for future drugs. In addition, the association between the various outcomes can aid in determining benefit when surrogate outcomes are used in approval consideration.
Objective
This study aims to (1) use the measures used in evaluating clinical trials by ESMO scores to determine the differences in the characteristics of 2013–2022 Food and Drug Administration (FDA) oncology NME drug approvals for those approved for use in combination or as a monotherapy, and (2) analyze the association between survival outcomes and the response rate for monotherapy NME drugs and/or drugs approved in combination.
Design
Cross-sectional analysis.
Setting
US FDA Oncology Drug Approvals (2013–2022)
Participants
US FDA Oncology Drug Approvals (2013–2022)
Exposures
Trial-level characteristics (tumor types, basis of approval, randomized or not, phase) and associations between overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) and whether NME drugs were approved as monotherapy or in combination .
Results
Drugs approved for use as a monotherapy are less likely to be approved using a randomized study (p < 0.001) and more likely to be approved via the accelerated pathway (p = 0.012) and be open-label (p < 0.001). Drugs approved for use as a combination or monotherapy significantly differed on their approval basis (p = 0.002), phase of trial at the time of approval (p = 0.02), and ESMO scores (p = 0.02). There was low correlation between response rate and either PFS or OS metrics. However, nearly all of the drugs with large improvements in OS (> 5months) were drugs with robust ORR.
Conclusions and relevance
Drugs approved as monotherapy with a low response rate are likely to have marginal benefit in OS and PFS.
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