Efficacy, Safety, and Regulatory Approval of Food and Drug Administration-Designated Breakthrough and Nonbreakthrough Cancer Medicines
Efficacy, Safety, and Regulatory Approval of Food and Drug Administration-Designated Breakthrough and Nonbreakthrough Cancer Medicines
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DOI：
10.1200/jco.2017.77.1592
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发表时间：
2018-06-20
影响因子：
45.3
通讯作者：
Darrow, Jonathan J.
中科院分区：
文献类型：
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作者：
Hwang, Thomas J.;Franklin, Jessica M.;Darrow, Jonathan J.
突破性治疗计划于2012年成立，旨在加快新药的开发和审查。我们评估的时间，以批准，疗效和安全性的突破指定与非突破指定的癌症药物批准美国食品和药物管理局（FDA）。MethodsWe研究了所有新的癌症药物批准的FDA在2012年1月至2017年12月。比较了突破性指定和非突破性指定癌症药物的监管和治疗特征（FDA批准时间、关键试验疗效终点、作用机制的新奇）。随机效应荟萃回归被用来评估突破性治疗指定和无进展生存期（PFS）的风险比之间的关联，反应率（RR）为实体瘤，严重不良事件，并不归因于疾病进展的死亡。ResultsBetween 2012 and 2017，FDA批准了58种新的癌症药物，其中25（43%）收到突破性治疗指定。突破性药物首次获得FDA批准的中位时间为5.2年，而非突破性药物为7.1年（差异为1.9年; P = 0.01）。突破性指定和非突破性指定药物在中位PFS增加（8.6 v4.0个月; P = 0.11）、PFS风险比（0.43 v0.51; P = 0.28）或实体瘤RR（37% v39%; P = 0.74）方面无统计学显著差异。突破性治疗指定药物不太可能通过新的作用机制发挥作用（36% vs 39%; P = 1.00）。死亡率（6%对4%; P = 0.99）和严重不良事件（38%v36%，P = 0.93）在突破性指定和非突破性指定的药物中也相似。结论突破性指定的癌症药物与更快的批准时间有关，但没有证据表明这些药物提供了安全性或新奇的改善;与非突破性指定药物相比，也没有统计学显著的疗效优势。
PurposeThe breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non-breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA).MethodsWe studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non-breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression.ResultsBetween 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non-breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non-breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy-designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non-breakthrough-designated drugs.ConclusionBreakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy advantage when compared with non-breakthrough-designated drugs.