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

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.

Grant Number: 5UH3CA260602-05
NIH Institute/Center: NIH
Principal Investigator: Christine Ambrosone