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: 10220449
• 负责人: Charles Stewart Kamen
• 金额: $ 105.99万
• 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/10220449
• 关键词: Address; Advanced Malignant Neoplasm; Affect; African; 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; Minority; 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; 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 免疫检查点抑制剂（ICI）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下降。其使用 在过去三年中急剧增加。然而，关于ICI治疗的数据很少 非洲血统（AA）患者的反应。此外，人们对它的毒性知之甚少， 治疗模式、长期结局和治疗后生活质量与外部ICI相关 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。 关注ICI影响的种族差异很重要，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，一个重要的疾病组ICI是 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， 促炎反应比EA。这可能导致免疫相关不良事件（irAE）的风险更高 在ICIs上。第三，由于免疫差异，管理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 获得医疗保健时的障碍（例如，歧视、财务毒性），可能导致ICI终止。 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AA患者对ICI的不同经验，通过通过 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，无论癌症部位如何，共招募600例AA和1，200例EA患者， 在NCORP研究中心内，AA与EA患者的癌症类型1：2匹配。我们的具体目标是： 1.检查irAE的种族差异和预测因素，比较AA和EA患者的发病率和 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停药，并评估种族 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，比较AA和EA患者的客观 缓解率（ORR）、复发、死亡和ICI后的HRQOL，并评估治疗、疾病， 个体和生活方式因素作为患者结局的预测因子和种族差异的潜在原因。 我们设想这将是第一个对接受ICI治疗的不同AA和EA患者进行的大型队列研究。我们将获得 社区肿瘤学环境中ICI的使用，效果和挑战的宝贵知识。我们的研究结果 可能为ICI的使用、irAE的管理和减少人群间的医疗保健障碍提供信息。