Systematic review and meta-analysis of cardiovascular adverse events with osimertinib therapy for non-small cell lung cancer

The incidences and specific risk fctors for cardiovascular adverse events (CVAEs) during osimertinib treatment for non-small cell lung cancer (NSCLC) are not clear. A systematic review and meta-analysis of 61 studies (10,316 NSCLC patients) investigated treatment-emergent and treatment-related CVAEs with osimertinib. Hypertension was the most common treatment-emergent and treatment-related CVAE, for both all-grade and grade ≥ 3. In addition to QTc prolongation (6.88%; 95% CI 5.24-8.70), there was also a common incidence of all-grade treatment-emergent LVEF decrease (4.31%; 95% CI 2.38-6.69). Subgroup analyses showed higher incidences of treatment-emergent than treatment-related hypertension in anti-VEGF combination therapy. QTc prolongation and LVEF reduction occurred more frequently with osimertinib plus platinum-pemetrexed than with other treatments. Univariable meta-regression further indicated that the cardiovascular toxicity profile of osimertinib was related to treatment regimens, while independent of age, race, and prior exposure to EGFR-TKIs. The authors conclude that hypertension is the most frequent treatment-emergent and treatment-related CVAE associated with osimertinib. Therapies combining anti-VEGF therapy present a particularly severe cardiac safety profile.