Tan Aaron C, Boggs Drexell H, Lee Eudocia Q, Kim Michelle M, Mehta Minesh P, Khasraw Mustafa
Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
Front Oncol. 2022 Jan 3;11:780379. doi: 10.3389/fonc.2021.780379. eCollection 2021.
Brain metastases cause significant morbidity and mortality in patients with advanced cancer. In the era of precision oncology and immunotherapy, there are rapidly evolving systemic treatment options. These novel therapies may have variable intracranial efficacy, and patients with brain metastases remain a population of special interest. Typically, only patients with stable, asymptomatic and/or treated brain metastases are enrolled in clinical trials, or may be excluded altogether, particularly in the setting of leptomeningeal carcinomatosis. Consequently, this leads to significant concerns on the external validity of clinical trial evidence to real-world clinical practice. Here we describe the current trends in cancer clinical trial eligibility for patients with brain metastases in both early and late phase trials, with a focus on targeted and immunotherapies. We evaluate recent newly FDA approved therapies and the clinical trial evidence base leading to approval. This includes analysis of inclusion and exclusion criteria, requirements for baseline screening for brain metastases, surveillance cerebral imaging and incorporation of trial endpoints for patients with brain metastases. Finally, the use of alternative sources of data such as real-world evidence with registries and collaborative studies will be discussed.
脑转移瘤在晚期癌症患者中会导致显著的发病率和死亡率。在精准肿瘤学和免疫治疗时代，全身治疗选择正在迅速发展。这些新型疗法的颅内疗效可能各不相同，而脑转移瘤患者仍然是一个备受关注的特殊群体。通常情况下，只有脑转移瘤稳定、无症状和/或经过治疗的患者才会被纳入临床试验，或者可能被完全排除，特别是在软脑膜癌病的情况下。因此，这引发了人们对临床试验证据在真实世界临床实践中的外部有效性的重大担忧。在此，我们描述了早期和晚期试验中脑转移瘤患者癌症临床试验资格的当前趋势，重点关注靶向治疗和免疫治疗。我们评估了最近美国食品药品监督管理局（FDA）批准的新疗法以及促成批准的临床试验证据基础。这包括对纳入和排除标准、脑转移瘤基线筛查要求、监测脑部成像以及脑转移瘤患者试验终点纳入情况的分析。最后，将讨论使用替代数据来源，如来自注册库和合作研究的真实世界证据。
