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: 10391553
• 负责人: Charles Stewart Kamen
• 金额: $ 100.42万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10391553
• 关键词: Address; Advanced Malignant Neoplasm; Affect; African ancestry; Aftercare; B-Lymphocytes; Behavioral; Cancer Patient; Cancer Survivor; Cells; Cessation of life; Clinical Trials; Cohort Studies; Community Clinical Oncology Program; Data; Diagnosis; Discrimination; Disease; Drops; Enrollment; Ensure; European; Frequencies; Funding; Goals; Healthcare; Immune; Immune checkpoint inhibitor; Immune response; Immunity; Immunotherapy; Incidence; Individual; Infiltration; Inflammatory; Inflammatory Response; Insurance; Interruption; Knowledge; Lead; Life Style; Link; Long-Term Effects; Malignant Neoplasms; Modality; Outcome; Patient-Focused Outcomes; Patients; Pattern; Population; Prospective cohort; Prospective cohort study; Quality of life; Race; Recurrence; Research; Safety; Sampling; Severities; 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-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 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.

摘要 免疫检查点抑制物(ICIS)是一种强大的创新癌症治疗模式，被认为是 部分原因是2016年至2017年癌症死亡率的最大单年降幅。它们的使用有 在过去的3年里急剧增加。然而，很少有关于ICI治疗的数据被收集。 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ICIS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。一项关注再生障碍性贫血患者种族差异的前瞻性队列研究 而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。 关注ICI影响中的种族差异很重要，原因有三。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是一种重要的疾病组 意在治疗。其次，由于宿主免疫的种族差异，再生障碍性贫血个体往往有更强的 促炎症反应优于EAs。这可能会导致更高的免疫相关不良事件(IrAEs)风险。 在ICIS上的时候。第三，由于免疫差异，管理irAEs和继续ICI的AA患者 治疗可能比电针患者更有可能受益。然而，再生障碍性贫血人群可能会经历多个 在获得医疗保健方面的障碍(例如，歧视、财务毒性)，这些障碍可能导致停止使用ICIS。 我们有一个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 这有助于再生障碍性贫血患者在ICIS上的不同体验，通过 全国NCI社区肿瘤学研究计划(NCORP)网络。我们将包括所有患者 接受抗PD-1/-L1治疗，不考虑肿瘤部位，共招募600名AA和1200名EA患者， 在NCORP部位，AA和EA患者的肿瘤类型1：2匹配。我们的具体目标是： 1.检验irAEs的种族差异和预测因素，比较AA和EA患者的发病率和 IrAEs的严重程度以及评估疾病、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患者的治疗延迟和中断情况，并评估种族 IrAEs、医疗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，比较AA和EA患者的客观情况 ICIS后的应答率(ORR)、复发、死亡和HRQOL，以及评估治疗、疾病、 个体和生活方式因素作为患者预后的预测因素和种族差异的潜在原因。 我们认为这将是首次对接受ICIS治疗的不同AA和EA患者进行的大型队列研究。我们会受益的 关于ICIS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 可为ICIS的使用、irAEs的管理和减少人群中的医疗壁垒提供信息。