文章目录

加性预测了大多数已批准的晚期癌症联合疗法的疗效

原文发布日期：2023-11-16

英文摘要：

摘要翻译：

原文链接：

文章：

加性预测了大多数已批准的晚期癌症联合疗法的疗效

Additivity predicts the efficacy of most approved combination therapies for advanced cancer

原文发布日期：2023-11-16

英文摘要：

Most advanced cancers are treated with drug combinations. Rational design aims to identify synergistic combinations, but existing synergy metrics apply to preclinical, not clinical data. Here we propose a model of drug additivity for progression-free survival (PFS) to assess whether clinical efficacies of approved drug combinations are additive or synergistic. This model includes patient-to-patient variability in best single-drug response plus the weaker drug per patient. Among US Food and Drug Administration approvals of drug combinations for advanced cancers (1995–2020), 95% exhibited additive or less than additive effects on PFS times. Among positive or negative phase 3 trials published between 2014–2018, every combination that improved PFS was expected to succeed by additivity (100% sensitivity) and most failures were expected to fail (78% specificity). This study shows synergy is neither a necessary nor common property of clinically effective drug combinations. The predictable efficacy of approved combinations suggests that additivity can be a design principle for combination therapies.

摘要翻译：

大多数晚期癌症是用药物联合治疗的。理性设计旨在确定协同组合，但现有的协同度量适用于临床前，而不是临床数据。在这里，我们提出了一个无进展生存（PFS）的药物加性模型，以评估批准的药物组合的临床疗效是加性的还是协同的。该模型包括最佳单药反应的患者与患者之间的差异以及每个患者较弱的药物。在美国食品和药物管理局批准的晚期癌症药物组合中（1995-2020），95%的药物对PFS时间表现出相加或小于相加的效应。在2014-2018年发表的阳性或阴性3期试验中，通过加和性（100%的敏感性）预计每个改善PFS的组合都将成功，大多数失败预计将失败（78%的特异性）。本研究表明，协同作用既不是临床有效药物组合的必要条件，也不是共同特性。经批准的联合疗法的可预测疗效表明，可加性可作为联合疗法的设计原则。