CDK4/6 inhibitor toxicity in geriatric subgroups: Evidence from the FAERS database.

12126 Background: Despite their widespread use, the safety of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in geriatric patients remains underexplored. Methods: We conducted a retrospective analysis of cases reported in the FAERS database regarding CDK4/6i in female breast cancer patients from January 1, 2015, to September 30, 2024, focusing on hematological, gastrointestinal (GI), and liver toxicities. The cases were categorized into different age subgroups. Results: We identified 46,871 female patients with breast cancer treated with CDK4/6i (abemaciclib, n = 3,987 [8.5%]; palbociclib, n = 37,020 [79.0%]; ribociclib, n = 5,864 [12.5%]). According to multivariate analysis considering age subgroups, CDK4/6i type, and concomitant treatments, 75-84 age group had a lower risk of hematologic toxicity (OR = 0.93 [95% CI 0.86–1.00]; P = 0.040), with a similar trend identified in patients aged ≥85 years (OR = 0.88 [0.76–1.01)]; P = 0.077). Ribociclib was associated with a higher risk of hematologic toxicity (OR = 1.31 [1.17–1.47]; P < 0.0001), whereas palbociclib was associated with a reduced risk (OR = 0.90 [0.82–1.00]; P = 0.041). However, only 75-84 age group treated with abemaciclib (OR = 0.57 [0.41–0.77]) and ≥85 years group treated with palbociclib (OR = 0.85 [0.73–0.99]) showed a reduced risk compared to patients younger than 65, while no significant differences were found among age subgroups treated with ribociclib. Despite the overall higher risk of GI toxicity associated with abemaciclib (OR = 7.53 [6.65–8.56]; P < 0.0001), ≥85 years group showed a lower risk compared to patients younger than 65 (OR = 0.59 [0.38–0.88]). The overall risk of GI toxicity was also higher in patients treated with palbociclib compared to ribociclib (OR = 1.17 [1.04–1.31]), with no significant differences observed among the age subgroups. Among patients treated with ribociclib, 65–74 (OR = 1.33 [1.03–1.71]) and 75–84 (OR = 1.45 [1.06–1.96]) age groups showed a higher risk of GI toxicity, while no significant difference was observed in ≥85 years group (OR = 1.64 [0.79–3.04]). Ribociclib was associated with a higher risk of liver toxicity (OR = 1.37 [1.20–1.55]; P < 0.0001), whereas palbociclib was associated with a reduced risk (OR = 0.30 [0.27–0.34]; P < 0.0001). In both palbociclib- and ribociclib-treated patients, all geriatric age subgroups showed a reduced risk of liver toxicity (Palbociclib; 65-74 y, OR = 0.80 [0.70–0.91]; 75-84 y, OR = 0.49 [0.41–0.58]; ≥85 y, OR = 0.35 [0.23–0.51]; Ribociclib; 65-74 y, OR = 0.80 [0.67–0.96]; 75-84 y, OR = 0.51 [0.38–0.65]; ≥85 y, OR = 0.52 [0.25–0.95]). However, only 75-84 age group treated with abemaciclib (OR = 0.70 [0.49–0.97]) showed a reduced risk of liver toxicity. Conclusions: Our findings demonstrated that liver toxicity was lower across all geriatric age subgroups, and hematological toxicity was reduced only in 75-84 age group. There were no significant differences in GI toxicities among the age subgroups.