Incidence, Management, and Clinical Outcomes of Cardiovascular Adverse Events in Patients Receiving ALK Inhibitors for Advanced Non-Small Cell Lung Cancer: A Real-World Single-Center Analysis

Abstract

Cardiovascular adverse event (CVAE) profiles across ALK-TKI generations remain incompletely characterized in real-world practice. A retrospective study of 235 ALK-rearranged NSCLC patients receiving first-, second-, or third-generation ALK-TKIs assessed CVAE incidence, severity, timing, management, and impact on progression-free survival (PFS). Sixty patients (25.5%; 95% CI, 20.4-31.5) experienced 72 CVAEs. Bradycardia (12.8%) was most common. Overall CVAE incidence did not differ between first- (26.9%) and second-/third-generation (25.0%) agents. Hypertension was numerically more frequent with later-generation agents (9.5% vs. 1.5%; uncorrected P = 0.047), but this difference did not remain significant after correction for multiple comparisons and should be regarded as exploratory; in agent-level analysis hypertension was most frequent with lorlatinib (35.0%). Median time to onset was 44 days. Thromboembolic events were the most severe category (71.4% grade ≥3) with the lowest resolution rate (57.1%), whereas 87.5% of all CVAEs resolved or improved. CVAE occurrence was not significantly associated with PFS (time-dependent adjusted HR 1.05; 95% CI, 0.74-1.48), a finding robust across fully adjusted and switch-excluded sensitivity models. ALK-TKIs carry a meaningful CVAE burden with generation- and agent-specific profiles. Risk-adapted monitoring aligned with temporal and pharmacological characteristics may improve management without compromising oncologic outcomes.