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.

PROJECT NARRATIVE Immune checkpoint inhibitors (ICIs) are new cancer immunotherapy agents that are effective in treating some advanced and metastatic cancers and improve the likelihood of patients living with the disease. Since we still know little about their survivorship needs, we aim to characterize the long-term survival and physical and psychosocial symptom trajectories of patients treated with ICIs for advanced and metastatic cancer. Our findings are expected to provide much-needed data that can inform new evidence-based intervention strategies to optimize cancer survivorship care for these patients.