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

6597 Background: Advances in breast cancer treatment have led to improvements in survival among patients with metastatic breast cancer (MBC). Nevertheless, Black patients and patients with lower socioeconomic status (SES) continue to bear a disproportionate mortality burden. Furthermore, because landmark trials for novel anticancer agents lacked racial diversity, their toxicity profile for minority patients remains uncertain. Our study examines the impact of race and other sociodemographic characteristics in the use and toxicity outcomes of PI3K and mTOR inhibitors (PI3K/mTORi). Methods: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database (FHD). A dataset was constructed to include patients with hormone receptor-positive, HER2-negative MBC diagnosed between 1/1/2011 and 1/31/2022. Outcomes included PI3K/mTORi use, rates of hyperglycemia and dose reduction, and time on treatment. Multivariable logistic regression was used to evaluate factors associated with use and outcomes. Results: A total of 13,388 patients with MBC were included in our analysis, of which 2,620 (19.6%) received PI3K/mTORi (78.3% everolimus, 14.7% alpelisib, 6.9% both agents). Overall, 67.5% of all patients were categorized as White, 9.8% as Black/African-American (Black/AA); 18.9% were >75 years old; 10.1% were treated at an academic site; 4.0% had Medicaid insurance. Insurance through Medicaid was associated with lower use of PI3K/mTORi compared to commercial insurance (15.6% vs 18.8%; OR: 0.76, 95% CI: 0.59-0.99, p=0.04), as was advanced age (10.9% for >75 years old vs 22.9% for <60 years old; OR: 0.68, 95% CI: 0.58-0.80, p<0.001) and poorer performance status at diagnosis (15.1% for ECOG ≥2+ vs 22.9% for ECOG 0; OR: 0.84, CI: 0.72-0.98, p=0.03). Odds of PI3K/mTORi use were almost 50% higher for patients treated at an academic center (OR: 1.46, CI: 1.06-2.05, p=0.02). While Black/AA patient had lower rates of use than White patients (17.4% vs 20.1%), they had similar odds of receiving PI3K/mTORi on multivariable analysis (OR: 1.00, CI: 0.85-1.17, p>0.9). Black/AA patients experienced higher rates of hyperglycemia on PI3K/mTORi than White patients (67.6% vs 52.5%). On multivariable analysis, odds of hyperglycemia were twice as high for Black/AA patients (OR: 2.1, CI: 1.33-3.35, p<0.01). However, rates of dose reductions and time on PI3K/mTORi therapy did not differ significantly among White vs Black/AA patients. Conclusions: This analysis of real-world data suggests that lower SES is associated with decreased PI3K/mTORi use. Efforts to improve access to these life-prolonging agents are warranted. Of concern, we also found racial disparities in toxicity outcomes, with Black patients having twice the risk of hyperglycemia. Greater attention to the tolerability of novel agents in diverse populations is warranted.