Breakthrough Therapy Cancer Drugs and Indications With FDA Approval: Development Time, Innovation, Trials, Clinical Benefit, Epidemiology, and Price.

IF 14.8 2区医学 Q1 ONCOLOGY

Journal of the National Comprehensive Cancer Network Pub Date : 2024-04-22 DOI:10.6004/jnccn.2023.7110

Daniel Tobias Michaeli, Thomas Michaeli

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引用次数: 0

Abstract

Background: The breakthrough therapy designation (BTD) facilitates the development of drugs with a large preliminary benefit in treating serious or life-threatening diseases. This study analyzes the FDA approval, trials, benefits, unmet needs, and pricing of breakthrough and nonbreakthrough therapy cancer drugs and indications.

Patients and methods: We analyzed 355 cancer indications with FDA approval (2012-2022). Breakthrough and nonbreakthrough indications were compared regarding their FDA approval, innovativeness, clinical trials, epidemiology, and price. Data were extracted from FDA labels, the Global Burden of Disease study, and the Centers for Medicare & Medicaid Services. Hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), and relative risk (RR) of tumor response were meta-analyzed across randomized controlled trials. Objective response rates (ORRs) were meta-analyzed for single-arm trials.

Results: We identified 137 breakthrough and 218 nonbreakthrough cancer indications. The median clinical development time was 3.2 years shorter for breakthrough drugs than for nonbreakthrough drugs (5.6 vs 8.8 years; P=.002). The BTD was more frequently granted to biomarker-directed indications (46% vs 34%; P=.025) supported by smaller trials (median, 149 vs 326 patients; P<.001) of single-arm (53% vs 27%; P<.001) and phase I or II design (61% vs 31%; P<.001). Breakthrough indications offered a greater OS (HR, 0.69 vs 0.74; P=.031) and tumor response (RR, 1.48 vs 1.32; P=.006; ORR, 52% vs 40%; P=.004), but not a PFS benefit (HR, 0.53 vs 0.58; P=.212). Median improvements in OS (4.8 vs 3.2 months; P=.002) and PFS (5.4 vs 3.3 months; P=.005) but not duration of response (8.7 vs 4.7 months; P=.245) were higher for breakthrough than for nonbreakthrough indications. The BTD was more frequently granted to first-in-class drugs (42% vs 28%; P=.001) and first-in-indication treatments (43% vs 29%; P<.001). There were no differences in treatment and epidemiologic characteristics between breakthrough and nonbreakthrough drugs. Breakthrough drugs were more expensive than nonbreakthrough drugs (mean monthly price, $38,971 vs $22,591; P=.0592).

Conclusions: The BTD expedites patient access to effective and innovative, but also expensive, new cancer drugs and indications.

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获得 FDA 批准的突破性治疗癌症药物和适应症：开发时间、创新、试验、临床疗效、流行病学和价格。

背景：突破性疗法认定（BTD）有助于开发在治疗严重或危及生命的疾病方面具有巨大初步疗效的药物。本研究分析了 FDA 批准、试验、收益、未满足的需求以及突破性和非突破性治疗癌症药物和适应症的定价：我们分析了获得 FDA 批准的 355 种癌症适应症（2012-2022 年）。比较了突破性和非突破性适应症在 FDA 批准、创新性、临床试验、流行病学和价格方面的情况。数据提取自 FDA 标签、全球疾病负担研究以及美国医疗保险与医疗补助服务中心。对随机对照试验的总生存期（OS）、无进展生存期（PFS）和肿瘤反应相对风险（RR）的危险比（HRs）进行了元分析。对单臂试验的客观反应率（ORR）进行了荟萃分析：我们确定了 137 个突破性癌症适应症和 218 个非突破性癌症适应症。突破性药物的中位临床开发时间比非突破性药物短 3.2 年（5.6 年 vs 8.8 年；P=.002）。生物标志物导向的适应症（46% 对 34%；P=.025）在较小规模试验（中位数为 149 例患者对 326 例患者；P=.025）的支持下更常获得 BTD：BTD 加快了患者获得有效、创新但也昂贵的癌症新药和适应症的速度。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of the National Comprehensive Cancer Network ONCOLOGY-

CiteScore

20.20

自引率

0.00%

发文量

388

审稿时长

4-8 weeks

期刊介绍： JNCCN—Journal of the National Comprehensive Cancer Network is a peer-reviewed medical journal read by over 25,000 oncologists and cancer care professionals nationwide. This indexed publication delivers the latest insights into best clinical practices, oncology health services research, and translational medicine. Notably, JNCCN provides updates on the NCCN Clinical Practice Guidelines in Oncology® (NCCN Guidelines®), review articles elaborating on guideline recommendations, health services research, and case reports that spotlight molecular insights in patient care. Guided by its vision, JNCCN seeks to advance the mission of NCCN by serving as the primary resource for information on NCCN Guidelines®, innovation in translational medicine, and scientific studies related to oncology health services research. This encompasses quality care and value, bioethics, comparative and cost effectiveness, public policy, and interventional research on supportive care and survivorship. JNCCN boasts indexing by prominent databases such as MEDLINE/PubMed, Chemical Abstracts, Embase, EmCare, and Scopus, reinforcing its standing as a reputable source for comprehensive information in the field of oncology.