1625P Cyclin-dependent kinase 4/6 inhibitors (CDKI)-associated venous thromboembolism in patients with hormone receptor (HR)-positive breast cancer

Abstract

Cyclin dependent kinases especially CDK 4/6 were shown to confer hormone therapy resistance in patients with breast cancer (BC). CDKI plus endocrine therapy (ET) has shown significant anti-tumor activity and survival advantage in patients with HR-positive BC and three CDKI are currently approved by the US FDA. The recent approval of abemaciclib in the adjuvant setting further heightened interest in the use of CDKI, yet CDKI-associated venous thromboembolism (VTE) remains notable. Hereby, we conducted an updated meta-analysis of randomized controlled trials (RCTs) to determine the risk of VTE in patients with BC. MEDLINE, EMBASE databases and meeting abstracts from inception through March 2022 were searched. RCTs that mentioned deep vein thrombosis and pulmonary embolism as adverse effect were incorporated in the analysis. Heterogeneity was assessed with Cochran's Q-statistic. The primary meta-analytic approach was random effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR) and risk difference (RD) with 95% confidence interval (CI). Ten phase 3 RCTs and four phase 2 studies with a total of 16,871 patients were eligible. Three CDKI (palbociclib, ribociclib, and abemaciclib) were employed across the studies. The VTE incidence was 217 (2.4%) in CDKI arm vs 63 (0.8%) control groups, respectively. The pooled RR for VTE was 2.33 (95%CI:1.37–3.97, P=0.002) and the absolute RD was 0.01 (95%CI: 0.01–0.02, P<0.0001). Further subgroup analyses demonstrated that there was statistically significant increase in VTE in patients with metastatic (RR,2.24; 95%CI:1.10–4.53, P=0.03), early BC (RR,2.95; 95%CI:1.48–5.89, P=0.002), patients receiving first-line therapy in metastatic BC (RR,2.52; 95%CI:1.16–5.44, P=0.02), patients receiving non-fulvestrant ET (RR,2.47; 95%CI:1.43–4.26, P=0.001), palbociclib (RR,2.12; 95%CI:1.17–3.82, P=0.01), and abemaciclib (RR,3.96; 95%CI:1.75–8.98, P=0.001). Patients on CDKI experienced a notable increase in the risk of VTE, compared to control arm. Vigilant monitoring on the risks of VTE and timely intervention once VTE develops, while receiving CDKI remain crucial.