Abstract PS5-06-25: Investigating association of comorbidities and race with all-cause mortality outcomes of PI3K inhibitor use in metastatic breast cancer (mBC)

PI3K and AKT pathway inhibitors Alpelisib, Inavolisib, and Capivasertib (PI3K/AKTi) are FDA approved treatments with demonstrated significant clinical benefit, improving progression free survival for Hormone receptor positive (HR+) mBC. Hyperglycemia can commonly develop from these agents. While knowledge about disparities in outcomes based on race and comorbidities in certain mBC subtypes is emerging, real world data about PI3K/AKTi is limited. In this propensity score-matched cohort study we used TriNetX de-identified EHR data from multiple health systems to compare mortality of patients with breast cancer diagnoses treated with PI3K/AKTi. We identified 2372 patients, female (F) and male (M), stratified in African American (AA; n= 262F, 8M), White (W; n=1933 F, 25M) and Asian (A, n=144F) cohorts. Qualification into the three race-based cohorts required presence of a C50 ICD-10-CM diagnosis code and treatment with PI3K/AKTi. Mortality outcomes were also compared in separate cohorts examining hazard ratios for conditions developed before or after treatment: diabetes (E08-E13), hypertension (I10-I15), obesity (E66), and hyperlipidemia (E78.4-5). Cohorts were matched for age, comorbidities, and treatment lines using 1:1 matching with a greedy nearest neighbor search. All-time Odds ratios (OR) and/or Hazard ratios (HR) with 95% confidence intervals are reported as an effect size and significance estimation. Compared to non-diabetic patients, those diagnosed with diabetes after treatment had higher odds of mortality post-matching (OR = 1.53, 95% CI 1.19-1.97), but those with pre-existing diabetes showed no significant difference in mortality (matched OR = 1.19, 95% CI 0.97-1.45). Both pre-existing hypertension and hypertension diagnosed post-treatment were associated with higher mortality compared to non-hypertensive patients: matched ORs = 1.23 (95% CI 1.02-1.47) and 2.02 (95% CI 1.36-3.00), matched HRs = 1.204 (95% CI 1.05-1.38) and 1.911 (95% CI 1.42-2.57), respectively. No statistically significant difference in mortality odds was seen comparing the AA cohort to W cohort (matched OR = 0.99, 95% CI 0.70-1.39) or A cohort to W cohort post matching (OR = 0.72, 95% CI 0.45-1.16). New-onset hyperlipidemia was not statistically significant after matching (OR = 1.15, 95% CI 0.91-1.45; HR = 1.15, 95% CI 0.97-1.35). No significant association was seen with obesity before or after treatment (all CI including 1). This study demonstrates that hypertension diagnosed before and after treatment with PI3K/AKTi is associated with higher mortality, as is diabetes diagnosis post-treatment. We did not identify disparities in mortality between our 3 racial cohorts. Future studies are needed to understand interactions between individual PI3K/AKTi agents and comorbidities to inform appropriate management strategies and ultimately improve patient outcomes. Citation Format: T. S. Morales, A. Strong, J. Petucci, M. K. Vasekar. Investigating association of comorbidities and race with all-cause mortality outcomes of PI3K inhibitor use in metastatic breast cancer (mBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-25.