Disparities in REsults of Immune Checkpoint Inhibitor Treatment (DiRECT): A Prospective Cohort Study of Cancer Survivors Treated with anti-PD-1/anti-PD-L1 in a Community Oncology Setting

免疫检查点抑制剂治疗 (DiRECT) 结果的差异：在社区肿瘤学环境中接受抗 PD-1/抗 PD-L1 治疗的癌症幸存者的前瞻性队列研究

• 批准号: 10883853
• 负责人: Charles Stewart Kamen
• 金额: $ 249.49万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10883853
• 关键词: Address; Advanced Malignant Neoplasm; Affect; African ancestry; Aftercare; B-Lymphocytes; Behavioral; Cancer Patient; Cancer Survivor; Cessation of life; Clinical Trials; Cohort Studies; Community Clinical Oncology Program; Data; Diagnosis; Discrimination; Disease; Disparity; Drops; Enrollment; European ancestry; Frequencies; Funding; Goals; Healthcare; Immune; Immune checkpoint inhibitor; Immune response; Immunity; Immunotherapy; Incidence; Individual; Inflammatory; Inflammatory Response; Insurance; Interruption; Knowledge; Life Style; Link; Long-Term Effects; Malignant Neoplasms; Modality; Outcome; Patient-Focused Outcomes; Patients; Population; Prospective cohort; Prospective, cohort study; Quality of life; Race; Recurrence; Research; Safety; Severities; Shapes; Site; T-Lymphocyte; Time; Tissues; Toxic effect; Treatment outcome; anti-PD-1; anti-PD-1/PD-L1; anticancer research; cancer site; cancer therapy; cancer type; checkpoint therapy; cohort; cost; design; disorder subtype; exhaust; experience; fighting; financial toxicity; health care availability; health related quality of life; high risk; immune cell infiltrate; immune-related adverse events; innovation; lifestyle factors; minority patient; mortality; objective response rate; programmed cell death protein 1; programs; psychological distress; racial difference; response; side effect; social health determinants; standard of care; treatment pattern; treatment response; tumor; tumor microenvironment; uptake

ABSTRACT Immune checkpoint inhibitors (ICIs) are a powerful and innovative mode of cancer therapy, believed to be partially responsible for the largest single-year drop in cancer mortality from 2016 to 2017. Their use has increased dramatically over the past 3 years. However, little data has been collected about ICI treatment response among patients of African ancestry (AA). In addition, little is known about the toxicities, treatment patterns, long-term outcomes, and post-treatment quality of life associated with ICIs outside the clinical trials setting. A prospective cohort study with a focus on racial differences between AA patients and patients of European ancestry (EA) in community oncology settings could address these knowledge gaps. Focusing on racial differences in ICI impact is important for three reasons. First, at the population level, AA patients are more likely than EA patients to have advanced cancers, an important disease group ICIs are intended to treat. Second, due to racial differences in host immunity, AA individuals tend to have a stronger pro-inflammatory response than EAs. This could lead to a higher risk of immune-related adverse events (irAEs) while on ICIs. Third, as a result of immune differences, AA patients who manage irAEs and continue ICI treatment may be more likely to benefit than EA patients. However, AA populations may experience multiple barriers while accessing healthcare (e.g., discrimination, financial toxicity) that may lead to discontinuing ICIs. We have a unique opportunity to assess the treatment, disease, individual, lifestyle, and quality of life factors that contribute to differential experiences of AA patients on ICIs, by accruing a prospective cohort through the nationwide NCI Community Oncology Research Program (NCORP) network. We will include all patients receiving anti-PD-1/-L1 therapy regardless of cancer site and enroll a total of 600 AA and 1,200 EA patients, with 1:2 match of AA to EA patients on cancer type within NCORP site. Our Specific Aims are: 1. To examine racial differences and predictors of irAEs, comparing AA and EA patients on incidence and severity of irAEs and assessing disease, individual, and lifestyle factors as predictors of these differences. 2. To examine treatment delay and discontinuation between AA and EA patients and assess racial differences in irAEs, healthcare barriers, and other factors as potential causes of treatment interruptions. 3. To examine short- and long-term treatment outcomes, comparing AA and EA patients on objective response rate (ORR), recurrence, death, and HRQOL after ICIs, and assessing treatment, disease, individual, and lifestyle factors as predictors of patient outcomes and potential causes of racial differences. We envision this to be the first large cohort study of diverse AA and EA patients treated with ICIs. We will gain valuable knowledge of the usage, effects, and challenges of ICIs in community oncology settings. Our findings may inform use of ICIs, management of irAEs and reduction of healthcare barriers across populations.

抽象的 免疫检查点抑制剂（ICIs）是一种强大且创新的癌症治疗模式，被认为是 2016 年至 2017 年癌症死亡率单年大幅下降的部分原因是它们的使用。 过去3年急剧增加。然而，关于 ICI 治疗的数据很少 非洲血统（AA）患者的反应。此外，人们对其毒性知之甚少， 与外部 ICI 相关的治疗模式、长期结果和治疗后生活质量 临床试验设置。一项关注 AA 患者种族差异的前瞻性队列研究 社区肿瘤学环境中的欧洲血统 (EA) 患者可以解决这些知识差距。 出于三个原因，关注 ICI 影响中的种族差异非常重要。首先，在人口层面，AA 患者比 EA 患者更有可能患有晚期癌症，ICIs 是一个重要的疾病组 旨在治疗。其次，由于宿主免疫力的种族差异，AA个体往往具有更强的免疫力。 促炎反应优于 EA。这可能会导致免疫相关不良事件 (irAE) 的风险更高 服用 ICI 时。第三，由于免疫差异，治疗 irAE 并继续 ICI 的 AA 患者 治疗可能比 EA 患者更有可能受益。然而，AA 人群可能会经历多种 获得医疗保健时遇到的障碍（例如歧视、经济毒性）可能会导致 ICI 的终止。 我们有独特的机会来评估治疗、疾病、个人、生活方式和生活质量因素 通过积累前瞻性队列，有助于 AA 患者对 ICI 的不同体验 全国 NCI 社区肿瘤​​学研究计划 (NCORP) 网络。我们将包括所有患者 无论癌症部位如何，都接受抗 PD-1/-L1 治疗，总共招募了 600 名 AA 和 1,200 名 EA 患者， AA 与 EA 患者在 NCORP 站点内的癌症类型上进行 1:2 匹配。我们的具体目标是： 1. 为了检查 irAE 的种族差异和预测因素，比较 AA 和 EA 患者的发生率和 irAE 的严重程度并评估疾病、个体和生活方式因素作为这些差异的预测因素。 2. 检查 AA 和 EA 患者之间的治疗延迟和中断情况并评估种族差异 irAE、医疗保健障碍和其他因素的差异是治疗中断的潜在原因。 3. 检查短期和长期治疗结果，客观比较 AA 和 EA 患者 ICI 后的缓解率 (ORR)、复发、死亡和 HRQOL，并评估治疗、疾病、 个人和生活方式因素作为患者结果的预测因素和种族差异的潜在原因。 我们预计这是第一个针对接受 ICI 治疗的不同 AA 和 EA 患者的大型队列研究。我们将收获 关于 ICI 在社区肿瘤学环境中的使用、效果和挑战的宝贵知识。我们的发现 可以为 ICI 的使用、 irAE 的管理以及减少人群中的医疗保健障碍提供信息。