Trajectories of patient-reported cognitive function and age-related conditions in a longitudinal observational trial of immune checkpoint inhibitor (ICI) treatment: The DiRECT Cohort.

12014 Background: ICIs have become a mainstay in cancer treatment, but their impact on patient-centered side effects such as decline in cognitive function and age-related conditions (e.g., nutritional status, mobility) has not been fully characterized. Black patients have also been underrepresented in prospective studies of ICIs. Prior research indicates that Black cancer patients have strong pro-inflammatory immune responses, which could affect the impact of ICI treatment on cognitive function and age-related conditions. Methods: The longitudinal DiRECT cohort (URCC21038, NCT05364086) was established to examine ICI outcomes and side effects in Black and White patients through the NCI Community Oncology Research Program (NCORP). Patients reported their cognitive function through the PROMIS-Cog and age-related conditions through the Geriatric 8 (G8), with assessments before (A1), after (A2), 6 months after (A3), and annually after (A4+) their first ICI infusion. A longitudinal mixed-effects model (LMEM) with an unstructured covariance matrix and assessment as a nominal factor was used to evaluate trajectories of the two outcome variables. The models were adjusted for cancer type, race, and age (<65, 65+), including interactions with assessment. Multiple comparisons were conducted with a Sidak adjustment to maintain an overall significance level of p<0.05. Results: A total of 1,677 patients enrolled between 04/01/2022 and 08/31/2024 were included in the analysis: mean age 64; 409 Black; 626 lung, 290 breast, 251 gastrointestinal, 240 genitourinary, 131 gynecologic, 72 head/neck cancers; modal cancer stage IV. In unadjusted models, statistically and clinically significant declines from A1 to A3 were found for both cognitive function (SE=-2.54, p<0.0001) and age-related conditions (SE=-0.70, p<0.0001), with no change from A3 to A4. Patients with breast cancer experienced the steepest declines in both outcomes (SE=-3.40, p<0.0001 and SE=-0.76, p<0.01, respectively). Black patients experienced a steeper decline in cognitive function than White patients, particularly from A1 to A2 (SE=-1.28, p=0.01). There was no significant difference in trajectory of functional status by race. Patients <65 experienced steeper declines in cognitive function and age-related conditions (SE=1.21, p=0.02 and SE=0.84, p=0.04, respectively); Black patients <65 had steeper declines in cognitive functioning than White patients <65 (SE=-1.55, p=0.02). Conclusions: Breast cancer patients on ICIs appear to experience poor trajectories of cognitive function and age-related conditions over the first 6 months of treatment, while Black patients, particularly those <65, experience poor trajectories in cognitive function. These findings can inform tailored and risk-stratified interventions to improve ICI side effects.