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期刊来源：JAMA

原文链接：https://doi.org/10.1001/jama.2024.2396

摘要内容如下：

重要性

美国食品和药物管理局（FDA）的加速审批途径允许根据被认为“合理可能”预测临床效益的替代措施的变化，批准治疗未满足的医疗需求的研究药物。然后需要进行批准后的临床试验，以确认这些药物是否提供临床益处。

目的

确定获得加速批准的癌症药物是否最终显示出临床益处，并评估转换为常规批准的基础。

设计、设置和参与者

在这项队列研究中，公开可用的FDA数据用于确定2013年至2023年获得加速批准的癌症药物。

主要成果和措施

在随访5年以上的加速批准中，生活质量或总生存率有所改善，以及药物适应症对转换为常规批准的验证性试验终点和转换时间。

结果

2013年至2023年，共有129个癌症药物适应症对获得加速批准。在46个随访超过5年的适应症中（2013-2017年批准），约三分之二（29，63%）转为常规批准，10个（22%）被撤销，7个（15%）在中位数为6.3年后仍在进行。不到一半（20/46，43%）的患者在验证性试验中显示出临床获益。退出时间从9.9年减少到3.6年，定期批准时间从1.6年增加到3.6年。在48个转换为常规批准的药物适应症对中，19个（40%）根据总生存期转换，21个（44%）根据无进展生存期转换，5个（10%）根据缓解率加缓解持续时间转换，2个（4%）根据缓解率转换，1个（2%）尽管有阴性验证性试验。比较加速和常规批准的适应症，48例中有18例（38%）没有变化，而48例中有30例（63%）有不同的适应症（例如，早期治疗）。

结论和相关性

在加速批准的5年内，大多数获得加速批准的癌症药物在总体生存或生活质量方面没有表现出益处。应明确告知患者使用加速审批途径的癌症药物，这些药物最终不会在以患者为中心的临床结果中显示出益处。

英文原文如下：

Abstracts

Importance  The US Food and Drug Administration's (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered "reasonably likely" to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical benefit.

Objective  To determine whether cancer drugs granted accelerated approval ultimately demonstrate clinical benefit and to evaluate the basis of conversion to regular approval.

Design, Setting, and Participants  In this cohort study, publicly available FDA data were used to identify cancer drugs granted accelerated approval from 2013 to 2023.

Main Outcomes and Measures  Demonstrated improvement in quality of life or overall survival in accelerated approvals with more than 5 years of follow-up, as well as confirmatory trial end points and time to conversion for drug-indication pairs converted to regular approval.

Results  A total of 129 cancer drug-indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and 7 (15%) remained ongoing after a median of 6.3 years. Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years. Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, 5 (10%) on response rate plus duration of response, 2 (4%) on response rate, and 1 (2%) despite a negative confirmatory trial. Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (eg, earlier line of therapy).

Conclusions and Relevance  Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.

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