PDF(Pubmed)
Abstract：
UNASSIGNED: In the era of precision oncology (PO), systemic therapies for patients (pts) with solid tumors have shifted from chemotherapy (CT) to targeted therapy (TT) and immunotherapy (IO). This systematic survey describes features of trials enrolling between 2010-2020, focusing on inclusion criteria, type of dose escalation scheme (DES) utilized, and use of expansion cohorts (ECs).
UNASSIGNED: A literature search identified phase I studies in adults with solid tumors published January 1, 2000 - December 31, 2020 from 12 journals. We included only studies enrolling between 2010-2020 to better capture the PO era. Two reviewers abstracted data; a third established concordance.
UNASSIGNED: Of 10,744 studies, 10,195 were non-topical or enrolled prior to 2010; 437 studies were included. The most common drug classes were TT (47.6%), IO (22%), and CT (6.9%). In studies which reported race, patients were predominantly white (61.7%) or Asian (25.7%), followed by black (6.5%) or other (6.1%). Heterogeneity was observed in the reporting and specification of study inclusion criteria. Only 40.1% of studies utilized ECs, and among the studies which used ECS, 46.6% were defined by genomic selection. Rule-based DES were used in 89% of trials; a 3+3 design was used in 80.5%. Of all drugs tested, 37.5% advanced to phase II, while 10.3% garnered regulatory licensure (for an indication tested in phase I).
UNASSIGNED: In the era of PO, TT and IO have emerged as the most studied agents in phase I trials. Rule-based DES, which are more relevant for escalating CT, are still chiefly utilized.
UNASSIGNED: A literature search identified phase I studies in adults with solid tumors published January 1, 2000 - December 31, 2020 from 12 journals. We included only studies enrolling between 2010-2020 to better capture the PO era. Two reviewers abstracted data; a third established concordance.
UNASSIGNED: Of 10,744 studies, 10,195 were non-topical or enrolled prior to 2010; 437 studies were included. The most common drug classes were TT (47.6%), IO (22%), and CT (6.9%). In studies which reported race, patients were predominantly white (61.7%) or Asian (25.7%), followed by black (6.5%) or other (6.1%). Heterogeneity was observed in the reporting and specification of study inclusion criteria. Only 40.1% of studies utilized ECs, and among the studies which used ECS, 46.6% were defined by genomic selection. Rule-based DES were used in 89% of trials; a 3+3 design was used in 80.5%. Of all drugs tested, 37.5% advanced to phase II, while 10.3% garnered regulatory licensure (for an indication tested in phase I).
UNASSIGNED: In the era of PO, TT and IO have emerged as the most studied agents in phase I trials. Rule-based DES, which are more relevant for escalating CT, are still chiefly utilized.
摘要：
目的在精准肿瘤学（PO）时代，实体瘤患者(pts)的全身治疗已从化疗(CT)转向靶向治疗(TT)和免疫治疗(IO).这项系统的调查描述了2010-2020年间注册试验的特点，重点是纳入标准，使用的剂量递增方案(DES)类型，和使用扩展队列(ECs)。方法通过文献检索，确定了2000年1月1日至2020年12月31日在12种期刊上发表的成人实体瘤I期研究。我们只纳入了2010-2020年之间注册的研究，以更好地捕捉PO时代。两名审阅者抽象了数据；第三个建立了一致性。10744项研究的结果,在2010年之前，有10,195项非局部研究或纳入；纳入了437项研究。最常见的药物类别是TT（47.6％），IO（22%），和CT（6.9%）。在报道种族的研究中，患者主要是白人（61.7％）或亚洲人（25.7％），其次是黑色(6.5%)或其他(6.1%)。在研究纳入标准的报告和规范中观察到异质性。只有40.1%的研究使用了ECs，在使用ECS的研究中，46.6%由基因组选择定义。89%的试验采用基于规则的DES；80.5%采用3+3设计。在所有测试的药物中，37.5%推进到第二阶段,而10.3%的人获得了监管许可(针对第一阶段测试的适应症)。结论在PO时代,TT和IO已成为I期试验中研究最多的药物。基于规则的DES，这与CT升级更相关，仍然主要被利用。
