乳腺癌药物：FDA 批准、开发时间、疗效、临床效益、创新、试验、终点、生活质量、价值和价格。

IF 4 3区医学 Q1 OBSTETRICS & GYNECOLOGY

Breast Cancer Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI:10.1007/s12282-024-01634-x

Julia Caroline Michaeli, Thomas Michaeli, Dario Trapani, Sebastian Albers, Dominik Dannehl, Rachel Würstlein, Daniel Tobias Michaeli

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引用次数: 0

摘要

目的：本研究分析了美国食品药品管理局（FDA）批准的乳腺癌新药的开发、效益、试验证据和价格：本研究分析了美国食品和药物管理局（FDA）批准的乳腺癌新药的开发、益处、试验证据和价格：我们确定了 26 种药物，42 种 FDA 批准的早期和转移性乳腺癌适应症（2000-2023 年）。数据收集自 FDA 标签、clinicaltrials.gov 以及 Medicare 和 Medicaid。对总生存期（OS）和无进展生存期（PFS）的危险比（HRs）以及肿瘤反应的相对风险（RR）和客观反应率（ORR）进行了荟萃分析：乳腺癌药物的中位研发时间为 7.8 年（95% CI 6.2-10.8）。26%的治疗药物被认为是创新药物（"首个适应症"），88%通过靶向机制发挥作用。64%为小分子药物，19%为抗体药物，18%为抗体药物共轭物。38%被批准用于HR+乳腺癌，31%用于HER2+乳腺癌。6个适应症用于早期乳腺癌，36个用于转移性乳腺癌。适应症采用了 FDA 的特殊计划：孤儿（2%）、快速通道（24%）、加速审批（19%）、优先审查（74%）、突破性治疗（44%）。批准主要由 3 期试验（88%）和随机对照设计（66%）支持，19 个国家（IQR 17-20）的 181 个中心（IQR 142-223）共招募了中位数为 585 名患者（IQR 417-752）。新药的 OS HR 为 0.78（95% CI 0.74-0.82），PFS 为 0.59（95% CI 0.54-0.64），肿瘤反应的 RR 为 1.61（95% CI 1.46-1.76）。OS和PFS的中位改善时间分别为2.8个月（IQR 1.8-5.8）和4.4个月（IQR 2.2-7.1）。在单臂试验中，平均 ORR 为 31% (95% CI 10-53)。在元回归中，OS/PFS之间的相关性为0.34（P = 0.031），OS/应答之间的相关性为0.01（P = 0.435）。60%的治疗获得了ESMO-MCBS "高价值 "评分，14%的治疗改善了生活质量。价格中位数为每月16,013美元（95% CI 13,097-17,617）。价格与患者获益之间没有关联。每延长一生命年的中位值为 62,419 美元（IQR 25,840-86,062 美元）：在过去的二十年里，创新有效药物的开发改变了乳腺癌患者的治疗格局。然而，研究人员和监管机构必须确保高价新药能够改善以患者为中心的临床终点：总生存期和生活质量。

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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Breast cancer drugs: FDA approval, development time, efficacy, clinical benefits, innovation, trials, endpoints, quality of life, value, and price.

Objective: This study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval.

Methods: We identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000-2023). Data were collected from FDA labels, clinicaltrials.gov, and Medicare and Medicaid. Overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) and tumor response's relative risk (RR) alongside objective response rate (ORR) were meta-analyzed.

Results: The median development time for breast cancer drugs was 7.8 years (95% CI 6.2-10.8). 26% of treatments were considered innovative ("first-in-indication") with 88% acting via a targeted mechanism. 64% were small molecules, 19% antibodies, and 18% antibody-drug conjugates. 38% were approved for HR + and 31% for HER2 + breast cancer. 6 indications were for early and 36 for metastatic breast cancer. Indications utilized FDA's special programs: orphan (2%), fast track (24%), accelerated approval (19%), priority review (74%), breakthrough therapy (44%). Approval was predominantly supported by phase 3 trials (88%) of randomized controlled design (66%), enrolling a median of 585 patients (IQR 417-752) at 181 centers (IQR 142-223) across 19 countries (IQR 17-20). New drugs' HR were 0.78 for OS (95% CI 0.74-0.82) and 0.59 for PFS (95% CI 0.54-0.64) with a RR for tumor response of 1.61 (95% CI 1.46-1.76). Median improvements of OS were 2.8 months (IQR 1.8-5.8) and PFS were 4.4 months (IQR 2.2-7.1). In single-arm trials, the average ORR was 31% (95% CI 10-53). In meta-regressions, the correlation between OS/PFS was 0.34 (p = 0.031) and OS/response was 0.01 (p = 0.435). 60% of treatments had a 'high-value' ESMO-MCBS score with 14% demonstrating improvements in quality of life. The median price was $16,013 per month (95% CI 13,097-17,617). There was no association between prices and patient benefit. The median value per life year gained was $62,419 (IQR 25,840-86,062).

Conclusions: Over the past two decades, the development of innovative and effective drugs transformed the treatment landscape for breast cancer patients. Yet, investigators and regulators must safeguard that highly-priced new drugs demonstrate improvements in patient-centered clinical endpoints: overall survival and quality of life.

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来源期刊

Breast Cancer ONCOLOGY-OBSTETRICS & GYNECOLOGY

CiteScore

6.70

自引率

2.50%

发文量

105

审稿时长

6-12 weeks

期刊介绍： Breast Cancer, the official journal of the Japanese Breast Cancer Society, publishes articles that contribute to progress in the field, in basic or translational research and also in clinical research, seeking to develop a new focus and new perspectives for all who are concerned with breast cancer. The journal welcomes all original articles describing clinical and epidemiological studies and laboratory investigations regarding breast cancer and related diseases. The journal will consider five types of articles: editorials, review articles, original articles, case reports, and rapid communications. Although editorials and review articles will principally be solicited by the editors, they can also be submitted for peer review, as in the case of original articles. The journal provides the best of up-to-date information on breast cancer, presenting readers with high-impact, original work focusing on pivotal issues.