Vascular events with immune checkpoint inhibitors in melanoma or non-small cell lung cancer: A systematic review and meta-analysis

The incidence of venous and arterial thromboembolic events in advanced cancer patients treated with immune checkpoint inhibitors (ICIs) has been sporadically reported. We performed a systematic review and meta-analysis to assess the rate of vascular events in patients with melanoma and non-small cell lung cancer (NSCLC) treated with ICIs. A systematic search of MEDLINE and EMBASE was performed to identify randomized clinical trials and prospective studies. The main outcomes were venous thromboembolism (VTE), stroke or systemic embolism (SE) and myocardial infarction (MI). Secondary outcomes were fatal VTE, fatal stroke or SE and fatal MI. Pooled proportions with 95% confidence intervals (CI) were calculated using random-effects models. A total of 59 trials, 25 in 5,578 patients with melanoma and 34 in 6,543 patients with NSCLC were included. In patients with melanoma, rates of VTE, stroke or SE and MI were 1.5% (95% CI 0.8–2.8), 1.7% (95% CI 0.8–3.7) and 0.4% (95% CI 0.2–0.9), respectively. In patients with NSCLC, corresponding rates were 1.9% (95% CI 1.2–3.2), 1.2% (95% CI 0.6–2.5), and 1.1% (95% CI 0.5–2.1), respectively. Rates of fatal VTE and MI were similar in melanoma and NSCLC patients. Rates of fatal stroke or SE were 1.9% (95% CI 0.4–9.5) and 0.7% (95% CI 0.2–2.3) in melanoma and NSCLC patients, respectively. Rates of VTE (3.1% vs. 1.1%) and myocardial infarction (3.4% Vs. 0.5%) were numerically higher in NSCLC patients treated with combined-ICIs vs mono-ICIs. Our study shows a not negligible rate of vascular events in patients with melanoma or NSCLC treated with ICIs.