分子靶点和 FDA 批准的基因组靶向癌症疗法的临床价值

IF 22.5 1区 医学 Q1 ONCOLOGY JAMA Oncology Pub Date : 2024-04-04 DOI:10.1001/jamaoncol.2024.0194
Ariadna Tibau, Thomas J. Hwang, Consolacion Molto, Jerry Avorn, Aaron S. Kesselheim
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From FDA drug labels and trial reports, key characteristics of pivotal trials were extracted, including the outcomes assessed.Main Outcomes and MeasuresThe strength of evidence supporting molecular targetability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit for their approved indications was evaluated using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS). Substantial clinical benefit was defined as a grade of A or B for curative intent and 4 or 5 for noncurative intent. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-based cancer treatments.ResultsA total of 50 molecular-targeted drugs covering 84 indications were analyzed. 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引用次数: 0

摘要

重要性基因组靶向抗癌新药的数量不断增加,为个性化治疗提供了可能,但成本往往很高.目的根据相应关键临床试验的结果,评估美国食品药品管理局批准的基因组靶向抗癌药物的分子靶点的有效性和治疗效果.设计和设置在这项队列研究中,分析了2015年1月1日至2022年12月31日期间获得美国食品药品管理局批准的所有基因组靶向抗癌药物.主要结果和测量方法采用欧洲学会的药物标签和试验报告,评估支持分子靶向性的证据的强度.主要结果和测量方法采用欧洲学会的药物标签和试验报告,评估支持分子靶向性的证据的强度.主要结果和测量方法采用欧洲学会的药物标签和试验报告,评估支持分子靶向性的证据的强度.主要结果和测量采用欧洲肿瘤内科学会(ESMO)分子靶点临床可操作性量表(ESCAT)评估支持分子靶向性的证据强度。采用ESMO-临床获益程度量表(ESMO-MCBS)评估其获批适应症的临床获益。实质性临床获益的定义是:治愈性临床获益达到 A 或 B 级,非治愈性临床获益达到 4 或 5 级。ESMO-MCBS将符合ESCAT类别I-A级和I-B级且具有实质性临床获益的分子靶点评定为高获益基因组癌症治疗方法。45个适应症(54%)是根据1期或2期关键试验批准的,45个适应症(54%)得到了单臂关键试验的支持,48个适应症(57%)是根据亚组分析批准的。在每个适应症中,84 个主要终点中有 46 个(55%)是总体反应率(中位数[IQR]总体反应率,57% [40%-69%];中位数[IQR]反应持续时间,11.1 [9.2-19.8] 个月)。在支持这84个适应症的84项关键试验中,38项试验(45%)具有I-A级ESCAT靶向性,32项试验(38%)具有I-B级靶向性。总体而言,84 项试验中有 24 项(29%)通过 ESMO-MCBS 证明了实质性临床获益。综合这些评级,84 项适应症中有 24 项(29%)与基于基因组的高获益癌症疗法有关。结论与相关性这项队列研究的结果表明,在最近批准的分子靶向癌症疗法中,只有不到三分之一的疗法在批准时显示出对患者的实质性获益。ESMO-MCBS和ESCAT等获益框架可以帮助医生、患者和支付方识别具有最大临床潜力的疗法。
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Clinical Value of Molecular Targets and FDA-Approved Genome-Targeted Cancer Therapies
ImportanceThe number of new genome-targeted cancer drugs has increased, offering the possibility of personalized therapy, often at a very high cost.ObjectiveTo assess the validity of molecular targets and therapeutic benefits of US Food and Drug Administration–approved genome-targeted cancer drugs based on the outcomes of their corresponding pivotal clinical trials.Design and SettingsIn this cohort study, all genome-targeted cancer drugs that were FDA-approved between January 1, 2015, and December 31, 2022, were analyzed. From FDA drug labels and trial reports, key characteristics of pivotal trials were extracted, including the outcomes assessed.Main Outcomes and MeasuresThe strength of evidence supporting molecular targetability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit for their approved indications was evaluated using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS). Substantial clinical benefit was defined as a grade of A or B for curative intent and 4 or 5 for noncurative intent. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-based cancer treatments.ResultsA total of 50 molecular-targeted drugs covering 84 indications were analyzed. Forty-five indications (54%) were approved based on phase 1 or phase 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials, and 48 (57%) were approved on the basis of subgroup analyses. By each indication, 46 of 84 primary end points (55%) were overall response rate (median [IQR] overall response rate, 57% [40%-69%]; median [IQR] duration of response, 11.1 [9.2-19.8] months). Among the 84 pivotal trials supporting these 84 indications, 38 trials (45%) had I-A ESCAT targetability, and 32 (38%) had I-B targetability. Overall, 24 of 84 trials (29%) demonstrated substantial clinical benefit via ESMO-MCBS. Combining these ratings, 24 of 84 indications (29%) were associated with high-benefit genomic-based cancer treatments.Conclusions and RelevanceThe results of this cohort study demonstrate that among recently approved molecular-targeted cancer therapies, fewer than one-third demonstrated substantial patient benefits at approval. Benefit frameworks such as ESMO-MCBS and ESCAT can help physicians, patients, and payers identify therapies with the greatest clinical potential.
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来源期刊
JAMA Oncology
JAMA Oncology Medicine-Oncology
自引率
1.80%
发文量
423
期刊介绍: JAMA Oncology is an international peer-reviewed journal that serves as the leading publication for scientists, clinicians, and trainees working in the field of oncology. It is part of the JAMA Network, a collection of peer-reviewed medical and specialty publications.
期刊最新文献
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