Péron Julien, Reverdy Thibaut, Smenteck Colette, Cortet Marion, You Benoît, Freyer Gilles
Service d'Oncologie Médicale, Institut de Cancérologie des Hospices Civils de Lyon, 69002 Lyon, France.
Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, CNRS UMR 5558, Université Claude Bernard Lyon 1, 69100 Villeurbanne, France.
Cancers (Basel). 2021 Jun 2;13(11):2757. doi: 10.3390/cancers13112757.
The benefit-risk assessments of new drugs for breast cancer (BC) face several challenges, as all stakeholders do not agree on the evidence bar required for market authorization, and by the fragmentation of breast cancer diagnosis. The aim of this study was to describe the changes in methods and designs of breast cancer confirmatory trials.
All phase III randomized trials published between 2001 and 2020 and assessing systemic BC therapies were included. Trials' main characteristics, endpoints, and statistical methods were collected using a standardized data extraction form.
A total of 347 randomized controlled trials (RCTs) met the inclusion criteria. While most older trials (79%) included all subtypes of breast cancer, most recent trials populations were limited to one large intrinsic BC subgroup (69%). The use of gatekeeping testing strategies increased dramatically from 9% to 71%. The use of overall survival (OS) as an endpoint in the trials increased over time, but its use as a primary endpoint remained infrequent. The inclusion of OS testing in a hierarchical sequence in case of positive testing of a tumor-centered or composite endpoint appeared to have become the new standard.
Our findings indicate some improvements in the quality of the evidence-base supporting new breast cancer drugs. The rigorous assessment of patient-relevant endpoints has increased over time, but this improvement is mainly related to the analysis of OS as a secondary endpoint analyzed in a hierarchical sequence.
乳腺癌新药的获益-风险评估面临诸多挑战，因为所有利益相关者对于市场授权所需的证据标准未达成一致，且乳腺癌诊断存在碎片化情况。本研究的目的是描述乳腺癌确证性试验的方法和设计的变化。
纳入2001年至2020年间发表的所有评估乳腺癌全身治疗的III期随机试验。使用标准化数据提取表收集试验的主要特征、终点和统计方法。
共有347项随机对照试验（RCT）符合纳入标准。虽然大多数早期试验（79%）纳入了所有乳腺癌亚型，但最近的试验人群仅限于一个大的内在性乳腺癌亚组（69%）。守门测试策略的使用从9%急剧增加到71%。试验中作为终点使用总生存期（OS）的情况随时间增加，但其作为主要终点的使用仍然不常见。在以肿瘤为中心的终点或复合终点呈阳性测试时将OS测试纳入分层序列似乎已成为新标准。
我们的研究结果表明，支持乳腺癌新药的证据基础质量有了一些改善。随着时间的推移，对与患者相关终点的严格评估有所增加，但这种改善主要与将OS作为分层序列中分析的次要终点的分析有关。
