Bleeding risk with concurrent anticoagulation and VEGF-TKI therapy in mRCC: A real-world TriNetX analysis.

Abstract

485 Background: Metastatic renal cell carcinoma (mRCC) is associated with both thromboembolic and hemorrhagic complications. VEGF-targeted tyrosine kinase inhibitors (TKIs); cabozantinib, lenvatinib, axitinib, and sunitinib are standard therapies, but their anti-angiogenic effects may heighten bleeding risk, particularly when combined with anticoagulants. Evidence guiding anticoagulation in this setting is limited, and clinical decisions remain challenging. We conducted a real-world analysis to evaluate bleeding risk with concurrent anticoagulation and VEGF-TKI therapy in mRCC. Methods: Using the TriNetX platform, we identified adults (≥18 years) with mRCC treated with cabozantinib, lenvatinib, axitinib, or sunitinib. Patients were grouped by anticoagulant use (rivaroxaban, apixaban, or warfarin) within 7 days before to 30 days after TKI initiation. Individuals who died before index were excluded. Propensity score matching (1:1) was applied for age and comorbidities. Bleeding events were assessed up to 1 year post-initiation; survival was analyzed up to 3 years. Results: After propensity matching: Lenvatinib: 132 patients per group; bleeding 25.0% vs 14.4% (RD 10.6%, p=0.03; RR 1.74, 95% CI 1.04–2.89); Axitinib: 284 per group; bleeding 20.4% vs 11.6% (RD 8.8%, p=0.004; RR 1.76, 95% CI 1.19–2.61); Sunitinib: 119 per group; bleeding 26.9% vs 9.3% (RD 17.7%, p=0.0004; RR 2.91, 95% CI 1.54–5.50); Cabozantinib: 470 per group; bleeding 18.1% vs 13.8% (RD 4.3%, p=0.07; RR 1.31, 95% CI 0.97–1.76). Bleeding was predominantly gastrointestinal; intracranial hemorrhage was rare. Survival was worse with anticoagulant use for lenvatinib (50% vs 37.1%, p=0.0348) and cabozantinib (53.96% vs 46.04%, p=0.0155); axitinib and sunitinib showed no significant survival differences. Conclusions: Concurrent anticoagulation with VEGF-TKIs in mRCC increases bleeding risk, particularly with sunitinib and axitinib, and to a lesser extent lenvatinib. Cabozantinib showed a non-significant trend. Most bleeding events were gastrointestinal. Survival was poorer among anticoagulant users on lenvatinib and cabozantinib. Clinicians should carefully weigh thrombosis prevention against bleeding risk and monitor closely. Personalized decision-making is essential in this high-risk population.