Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration
Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration
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DOI：
10.1002/cncr.33095
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发表时间：
2020-07-22
期刊：
影响因子：
6.2
通讯作者：
Tibau, Ariadna
中科院分区：
文献类型：
--
作者：
Molto, Consolacion;Hwang, Thomas J.;Tibau, Ariadna
突破性指定抗癌药物的临床获益和定价尚不确定。这项研究比较了新的和补充的突破性指定和非突破性指定癌症药物批准的临床效益和每月价格的大小。方法一个横断面队列，包括2012年7月至2017年12月批准用于实体瘤的癌症药物。对于每种适应症，通过经验证的框架对关键试验的临床获益进行评分：美国临床肿瘤学学会价值框架（ASCO-VF）、美国临床肿瘤学学会癌症研究委员会（ASCO-CRC）、欧洲医学肿瘤学学会临床获益量表（ESMO-MCBS）和国家综合癌症网络（NCCN）证据块。高临床获益定义为ASCO-VF评分>= 45，ASCO-CRC标准所有癌症类型的总生存期增加>= 2.5个月或无进展生存期增加>= 3个月，ESMO-MCBS治疗目的试验的A或B级，非治疗目的试验的4或5级，NCCN证据块的评分为4和5，组合评分>= 16。每月医疗保险药品价格计算与医疗保险价格和DrugAbacus。结果：本研究确定了106项试验，支持批准52种药物用于96种适应症。其中40%的迹象获得了突破性的认定。在纳入的试验中，分别有33项（43%）、46项（73%）、35项（34%）和67项（69%）符合ASCO-VF、ASCO-CRC、ESMO-MCBS和NCCN确定的阈值。在转移背景下，ASCO-VF支持突破性药物的试验中有更高的临床有意义的分级几率（比值比[OR]，3.69;P = .022）和NCCN证据块（OR，5.80;P = .003），但与ASCO-CRC（OR，3.54;P = .11）或ESMO-MCBS版本1.1（v1.1）（OR，1.22;P = .70）无关。突破性治疗药物的中位成本显著高于非突破性治疗药物（P = 0.001）。结论在晚期实体癌中，获得突破性治疗指定的药物比非突破性治疗药物更有可能被ASCO-VF和NCCN证据块评分为提供高临床获益，但不是ESMO-MCBS v1. 1或ASCO-CRC量表。
Background The clinical benefit and pricing of breakthrough-designated cancer drugs are uncertain. This study compares the magnitude of the clinical benefit and monthly price of new and supplemental breakthrough-designated and non-breakthrough-designated cancer drug approvals. Methods A cross-sectional cohort comprised approvals of cancer drugs for solid tumors from July 2012 to December 2017. For each indication, the clinical benefit from the pivotal trials was scored via validated frameworks: the American Society of Clinical Oncology Value Framework (ASCO-VF), the American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC), the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), and the National Comprehensive Cancer Network (NCCN) Evidence Blocks. A high clinical benefit was defined as scores >= 45 for the ASCO-VF, overall survival gains >= 2.5 months or progression-free survival gains >= 3 months for all cancer types for the ASCO-CRC criteria, a grade of A or B for trials of curative intent and a grade of 4 or 5 for trials of noncurative intent for the ESMO-MCBS, and scores of 4 and 5 and a combined score >= 16 for the NCCN Evidence Blocks. Monthly Medicare drug prices were calculated with Medicare prices and DrugAbacus. Results This study identified 106 trials supporting approval of 52 drugs for 96 indications. Forty percent of these indications received the breakthrough designation. Among the included trials, 33 (43%), 46 (73%), 35 (34%), and 67 (69%) met the thresholds established by the ASCO-VF, ASCO-CRC, ESMO-MCBS, and NCCN, respectively. In the metastatic setting, there were higher odds of clinically meaningful grades in trials supporting breakthrough drugs with the ASCO-VF (odds ratio [OR], 3.69;P = .022) and the NCCN Evidence Blocks (OR, 5.80;P = .003) but not with the ASCO-CRC (OR, 3.54;P = .11) or version 1.1 (v1.1) of the ESMO-MCBS (OR, 1.22;P = .70). The median costs of breakthrough therapy drugs were significantly higher than those of nonbreakthrough therapies (P = .001). Conclusions In advanced solid cancers, drugs that received the breakthrough therapy designation were more likely than nonbreakthrough therapy drugs to be scored as providing a high clinical benefit with the ASCO-VF and the NCCN Evidence Blocks but not with the ESMO-MCBS v1.1 or the ASCO-CRC scale.