Disparities in PI3K/mTOR inhibitor use, toxicities, and outcomes among patients with metastatic breast cancer

Purpose: Novel agents such as PI3K and mTOR inhibitors (PI3K/mTORi) have expanded treatment options in metastatic breast cancer (MBC). Nevertheless, mortality rates remain disproportionately high for Black patients and patients with lower socioeconomic status. Furthermore, clinical trials for these novel agents lacked diversity, so their toxicity profile in minority populations is uncertain. Methods: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database for patients with HR+, HER2− MBC. Multivariable logistic regression was used to evaluate factors associated with PI3K/mTORi use and toxicity outcomes. Results: A total of 9169 patients with MBC were included in our analysis, of which 1780 (19.4%) received a PI3K/mTORi. We estimated the conditional total effect of insurance through Medicaid, and found lower odds of use of PI3K/mTORi among patients on Medicaid compared to those with commercial insurance (OR 0.73, 95% CI 0.54–0.99, p = 0.049). Odds of PI3K/mTORi use were higher for patients treated at an academic center (OR 1.28, CI 1.06–1.55, p = 0.01). Modeled as a controlled direct effect, Black/African American (Black/AA) race had no impact on odds of PI3K/mTOR use. Black/AA patients had twice the odds of developing hyperglycemia on PI3K/mTORi compared to White patients (OR 2.02, CI 1.24–3.39, p < 0.01). Conclusion: This analysis of real-world data suggests that the use of PI3K/mTORi is influenced by socioeconomic factors. We also found racial disparities in toxicity outcomes, with Black/AA patients having twice the risk of hyperglycemia. Our findings call for greater efforts to ensure access to novel treatments and improve their tolerability in diverse populations.