To compare stroke proportions, subtypes, severity, and disproportionality across ICIs, targeted therapies, and cytotoxic chemotherapies in the U.S. FDA Adverse Event Reporting System (FAERS) from January 2011 to September 2025.

Immune checkpoint inhibitors (ICIs) have transformed oncology, including neuro-oncology, over the past decade, yet questions about cerebrovascular safety signals remain. Evaluating stroke reporting normalized to neurologic adverse events (AEs) provides a neuro-focused framework for assessing treatment-related risk.

FAERS was queried for stroke-related preferred terms, grouped as ischemic, hemorrhagic, or transient ischemic attack (TIA). Reports were categorized as ICIs (nivolumab, pembrolizumab, cemiplimab, atezolizumab, durvalumab, avelumab, ipilimumab, tremelimumab), targeted agents (cabozantinib, lenvatinib, bevacizumab), or cytotoxic chemotherapies (carboplatin, cisplatin, pemetrexed, etoposide). Stroke percentages were calculated relative to neurologic AEs (primary) and all AEs (secondary). Serious outcomes (hospitalization, death) and temporal trends were summarized. Disproportionality analyses (PRR, ROR, 95% CI) were performed with a 0.5 continuity correction.

Across pooled data, stroke comprised 1.63% of neurologic AEs for ICIs, 2.34% for targeted, 1.73% for cytotoxic, and 1.99% for combined chemo/targeted agents. Ischemic strokes predominated, followed by hemorrhagic and then TIA. Hospitalization and death occurred in 33–38% and 16–22% of stroke reports, respectively. Regarding disproportionality metrics, no pooled group met PRR ≥ 2 or ROR lower 95% CI > 1 under either denominator. Stroke reporting increased after 2016 with ICI adoption, while hemorrhagic/TIA proportions remained stable.

From January 2011 to September 2025, ICIs, targeted, and cytotoxic therapies showed comparable cerebrovascular reporting patterns when normalized to neurologic AEs. Consistent with past reported studies, ischemic events were most frequent, and although no disproportionality signals emerged, the substantial proportion of serious outcomes underscores the need for continued vigilance and prospective study of ICI-associated cerebrovascular risk.