A Multi-Institute Survivorship Study of Patients Living with Advanced Cancer Who Have Had Durable Response to Immune Checkpoint Inhibitors

对免疫检查点抑制剂有持久反应的晚期癌症患者的多机构生存研究

• 批准号: 10714336
• 负责人: Charles Stewart Kamen
• 金额: $ 81.59万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-14 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714336
• 关键词: Address; Adopted; Advanced Malignant Neoplasm; Age; Behavioral; Biological Markers; Body Composition; California; Cancer Center; Cancer Survivorship; Caring; Clinical; Communities; Companions; Comprehensive Cancer Center; Data; Diagnosis; Dimensions; Disease; Disease remission; Disseminated Malignant Neoplasm; Enrollment; Ethnic Origin; Evidence based intervention; FDA approved; Health behavior; Immune checkpoint inhibitor; Immune response; Immunotherapeutic agent; Immunotherapy; In complete remission; Inferior; Infusion procedures; Intervention; Learning; Life Style; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of lung; Metastatic Melanoma; Modeling; Mutation; Patient Care; Patient Outcomes Assessments; Patients; Phase; Population; Predictive Factor; Preparation; Prognosis; Progression-Free Survivals; Prospective cohort; Psychosocial Factor; Quality of life; Race; Renal carcinoma; Sister; Survivors; Symptoms; Telomere Length Maintenance; Therapeutic; Universities; Unresectable; advanced disease; behavioral health; cancer diagnosis; cancer immunotherapy; cancer therapy; cancer type; checkpoint therapy; clinical practice; clinical predictors; cohort; demographics; design; follow-up; improved; ipilimumab; melanoma; partial response; patient population; predictive marker; programmed cell death ligand 1; psychosocial; psychosocial wellbeing; racial disparity; response; sex; side effect; survival prediction; survivorship; tumor; Address; Adopted; Advanced Malignant Neoplasm; Age; Behavioral; Biological Markers; Body Composition; California; Cancer Center; Cancer Survivorship; Caring; Clinical; Communities; Companions; Comprehensive Cancer Center; Data; Diagnosis; Dimensions; Disease; Disease remission; Disseminated Malignant Neoplasm; Enrollment; Ethnic Origin; Evidence based intervention; FDA approved; Health behavior; Immune checkpoint inhibitor; Immune response; Immunotherapeutic agent; Immunotherapy; In complete remission; Inferior; Infusion procedures; Intervention; Learning; Life Style; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of lung; Metastatic Melanoma; Modeling; Mutation; Patient Care; Patient Outcomes Assessments; Patients; Phase; Population; Predictive Factor; Preparation; Prognosis; Progression-Free Survivals; Prospective cohort; Psychosocial Factor; Quality of life; Race; Renal carcinoma; Sister; Survivors; Symptoms; Telomere Length Maintenance; Therapeutic; Universities; Unresectable; advanced disease; behavioral health; cancer diagnosis; cancer immunotherapy; cancer therapy; cancer type; checkpoint therapy; clinical practice; clinical predictors; cohort; demographics; design; follow-up; improved; ipilimumab; melanoma; partial response; patient population; predictive marker; programmed cell death ligand 1; psychosocial; psychosocial wellbeing; racial disparity; response; sex; side effect; survival prediction; survivorship; tumor

ABSTRACT Immune checkpoint inhibitors (ICIs) have markedly transformed the therapeutic landscape for many types of advanced malignancies over the past decade. A sizable proportion of patients with advanced cancer derive durable benefits from ICIs and achieve longer periods of progression-free survival or remission than previously possible. Yet we still know little about the determinants of durable response to ICI treatment and the symptom trajectory and survivorship needs of this growing patient population. We thus propose a multi-institute study with two sister cohorts of patients living with advanced cancers. First, a retrospective EHR data-only cohort will include 8,860 patients with advanced disease, inclusive of all cancer types, who have been treated with ICI- based immunotherapy in 2014-2022. This large cohort will allow us to identify and study durable responders to ICIs, defined as patients who achieve partial or complete response to ICI treatment and live at least one year after ICI treatment initiation. Second, a prospective cohort will enroll and actively follow an estimated 1,200 patients with durable response to ICI treatment for advanced lung cancer, kidney cancer, and melanoma, the three most common cancers treated with ICIs. Clinical and patient-reported outcome data will be collected at baseline and every 6 months during follow up. This prospective cohort will allow us to study long-term survival and physical and psychosocial symptom trajectories in patients with durable response to ICIs, and to identify clinical and modifiable behavioral factors predictive of long-term survival and common side effects of ICI treatment. The predictors identified in these analyses will be independently validated in the DiRECT Cohort, a large ongoing study of racial disparities in ICI treatment led by the study team. Our Specific Aims are: 1. In the retrospective EHR data-only cohort, 1a) Determine the proportion of patients who had durable response to ICI treatment (partial/complete response and alive ≥1 year since initial ICI treatment) and chart their survival trajectory; 1b) Identify clinical predictors for durable response to ICI treatment; 1c). In the independent DiRECT Cohort, validate the clinical predictors for durable response to ICI treatment. 2. In the prospective cohort, 2a) Identify long-term survival and longitudinal trajectories of patients' physical and psychosocial symptoms after ICI treatment; 2b) Investigate the relationships of long-term survival and common side effects from ICI treatment with multidimensional predictors; 2c). In the independent DiRECT Cohort, validate the predictors for survival and common side effects in patients with durable response. Findings from our study will provide much-needed data that can inform new evidence-based intervention strategies as the next step to optimize survivorship care and extend and improve quality of life for the growing population of survivors living after a diagnosis of advanced cancer due to ICI treatment.

抽象的 免疫检查点抑制剂（ICI）已明显改变了许多类型的治疗景观 过去十年中的高级恶态。晚期癌症患者的相当比例很大 与以前相比 可能的。然而，我们仍然对ICI治疗持久反应​​的决定者和症状知之甚少 这个不断增长的患者人群的轨迹和生存需求。因此，我们提出了一项多个基础研究 有两名姐妹人群患有晚期癌症。首先，回顾性EHR仅数据组将 包括8,860例晚期疾病患者，包括所有癌症类型的患者 基于2014 - 2022年的免疫疗法。这个大型队列将使我们能够识别和研究耐用的响应者 ICIS，定义为对ICI治疗的部分或完全反应并至少生活一年的患者 在ICI治疗计划之后。其次，前瞻性队列将注册并积极遵循估计的1200 对ICI治疗治疗晚期肺癌，肾癌和黑色素瘤的持久反应的患者， 三种最常见的癌症接受ICIS治疗。将收集临床和患者报告的结果数据 后续过程中的基线和每6个月。这个前瞻性队列将使我们能够研究长期生存 以及对ICIS持久反应的患者的身体和社会心理症状轨迹，并确定 临床和可修改的行为因素可以预测长期生存和ICI的常见副作用 治疗。这些分析中确定的预测因素将在直接队列中独立验证 研究团队领导的ICI治疗中种族分布的大量研究。我们的具体目的是： 1。在回顾性EHR仅数据同类队列中，1A）确定持久患者的比例 对ICI治疗的反应（部分/完整反应和自初次ICI治疗以来≥1岁）和图表 他们的生存轨迹； 1b）确定对ICI治疗持久反应​​的临床预测因子； 1C）。在 独立的直接队列，验证临床预测因子对ICI治疗的持久反应。 2。在前瞻性队列中，2A）确定患者身体的长期生存和纵向轨迹 ICI治疗后的社会心理症状； 2b）研究长期生存和 ICI处理多维预测因子的常见副作用； 2C）。在独立直接 队列，验证持久反应患者的存活和常见副作用的预测因子。 我们研究的发现将提供急需的数据，可以为新的循证干预提供信息 策略是优化生存护理并延长和改善生活质量的下一步 因ICI治疗而导致晚期癌症诊断后的生存人群。