Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Sun Yat-sen Global Health Institute, School of Public Health and Institute of State Governance, Sun Yat-sen University, Guangzhou, China.
Int J Cancer. 2021 Jul 1;149(1):108-118. doi: 10.1002/ijc.33503. Epub 2021 Feb 22.
This cross-sectional and longitudinal descriptive analysis aimed to track the evolving landscape of global immuno-oncology (IO) trials and provide insight into the resolution of IO-related controversies. Clinical trials (n = 4510) registered on ClinicalTrials.gov in 2007 to 2019 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), cancer vaccines and immune modulators were included. Most of IO trials are Phase 2 and focus on ICIs and multiple IO therapies. The United States leads global IO research, with stable growth and the best methodological quality. Mainland China ranks first in the number of ACT trials but has the lowest article publication rate (6.2%). A multiple-arm comparative design is often adopted in multiple IO therapies trials (44.0%). Trials studying ICIs and multiple IO therapies are likely to use early registration (80.0% and 86.6%) and stringent corticosteroid-/infection-related criteria. Hospitals have provided the most extensive and strongest support for all IO categories. Big pharma prefers to fund Phase 3-4 ICI trials (6.98%), while small pharma has a wider sponsorship favoring Phase 1-2 trials. The "partial-use-of-corticosteroids" strategy is generally well accepted in ICI trials with a definitive trend (32.5%; P < .001) but is associated with the poor dissemination of results (P ≤ .020), while the complete disclosure and standardization of dose/timing limits are still lacking. Disparities in design features and dissemination of results are widespread in IO trials and are modulated by IO category, cancer type and sponsor. We propose policy reforms to redefine the timely publication of IO trials and standardize the resolution of corticosteroid-/infection-related issues.
本横断面和纵向描述性分析旨在追踪全球免疫肿瘤学（IO）试验的发展趋势，并深入了解 IO 相关争议的解决情况。纳入了 2007 年至 2019 年在 ClinicalTrials.gov 上注册的研究免疫检查点抑制剂（ICI）、过继细胞转移（ACT）、癌症疫苗和免疫调节剂的 4510 项临床试验。大多数 IO 试验为 2 期，重点研究 ICI 和多种 IO 疗法。美国引领全球 IO 研究，呈稳定增长态势，且方法学质量最佳。中国大陆 ACT 试验数量居世界首位，但文章发表率最低（6.2%）。在多项 IO 疗法试验中，通常采用多臂比较设计（44.0%）。研究 ICI 和多种 IO 疗法的试验更可能采用早期注册（80.0%和 86.6%）和严格的皮质类固醇/感染相关标准。所有 IO 类别均主要由医院提供最广泛和最强有力的支持。大型制药公司更倾向于资助 3 期-4 期 ICI 试验（6.98%），而小型制药公司的赞助范围更广，更倾向于 1 期-2 期试验。在 ICI 试验中，“部分使用皮质类固醇”策略总体上得到广泛认可（32.5%；P<.001），但与结果传播不佳有关（P≤.020），而剂量/时间限制的完全披露和标准化仍有待完善。IO 试验中设计特征和结果传播的差异普遍存在，并受 IO 类别、癌症类型和赞助商的调节。我们提出政策改革建议，重新定义 IO 试验的及时发表，并规范皮质类固醇/感染相关问题的解决。
