Oncology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, and Universitat Autònoma de Barcelona, Barcelona, Spain.
Program on Regulation, Therapeutics, and Law, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Cancer. 2020 Oct 1;126(19):4390-4399. doi: 10.1002/cncr.33095. Epub 2020 Jul 22.
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.
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.
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).
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.
突破性治疗药物的临床获益和定价尚不确定。本研究比较了新获批和补充获批的突破性和非突破性癌症治疗药物的临床获益程度和每月价格。
本研究为一项回顾性队列研究，纳入了 2012 年 7 月至 2017 年 12 月期间获批的实体瘤癌症药物。对于每种适应证，根据经过验证的框架对关键试验的临床获益进行评分：美国临床肿瘤学会价值框架（ASCO-VF）、美国临床肿瘤学会癌症研究委员会（ASCO-CRC）、欧洲肿瘤内科学会临床获益量表（ESMO-MCBS）和美国国家综合癌症网络（NCCN）证据块。高临床获益定义为 ASCO-VF 评分≥45 分、所有癌症类型的总生存期获益≥2.5 个月或无进展生存期获益≥3 个月的 ASCO-CRC 标准、有治愈意向的试验为 A 级或 B 级、无治愈意向的试验为 4 级或 5 级的 ESMO-MCBS 标准、以及 NCCN 证据块的评分≥4 分和 5 分且总评分≥16 分的标准。每月的医疗保险药物价格通过医疗保险价格和 DrugAbacus 计算。
本研究共纳入了 106 项支持 52 种药物获批 96 种适应证的临床试验。其中 40%的适应证获得了突破性治疗药物的认定。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 建立的标准。在转移性疾病环境中，具有 ASCO-VF（比值比[OR]，3.69；P=.022）和 NCCN 证据块（OR，5.80；P=.003）的突破性治疗药物试验更有可能具有有临床意义的等级，但 ASCO-CRC（OR，3.54；P=.11）或 ESMO-MCBS v1.1（OR，1.22；P=.70）并无此趋势。突破性治疗药物的中位费用明显高于非突破性治疗药物（P=.001）。
在晚期实体瘤中，与非突破性治疗药物相比，获得突破性治疗药物认定的药物更有可能通过 ASCO-VF 和 NCCN 证据块而不是 ESMO-MCBS v1.1 或 ASCO-CRC 标准被评为提供高临床获益。
