Cabozantinib Safety With Different Anticoagulants in Patients With Renal Cell Carcinoma

• Published in: Clinical genitourinary cancer 2023-02, Vol.21 (1), p.55-62
• Main Authors: Shayeb, Akram M., McManus, Hannah Dzimitrowicz, Urman, Danielle, Jani, Chinmay, Zhang, Tian, Dizman, Nazli, Meza, Luis, Sivakumar, Akhilesh, Gan, Chun L., Barata, Pedro, Bilen, Mehmet A., Gao, Xin, Heng, Daniel, Pal, Sumanta, Narra, Ravi, Kilari, Deepak, Kaymakcalan, Marina D., McGregor, Bradley, Choueiri, Toni K., McKay, Rana R.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Anticoagulants - adverse effects; Bleeding; Carcinoma, Renal Cell - complications; Carcinoma, Renal Cell - drug therapy; DOAC; Hemorrhage - chemically induced; Hemorrhage - complications; Hemorrhage - epidemiology; Heparin, Low-Molecular-Weight - adverse effects; Humans; Kidney Neoplasms - complications; Kidney Neoplasms - drug therapy; LMWH; Neoplasms - chemically induced; Neoplasms - complications; Neoplasms - drug therapy; Thrombosis; Venous Thromboembolism - drug therapy; VTE; Warfarin - adverse effects
• ISSN: 1558-7673; 1938-0682
• DOI: 10.1016/j.clgc.2022.10.013

•Data regarding direct oral anticoagulants (DOACs) appear safe for venous thromboembolism (VTE) treatment for patients with RCC on cabozantinib•No. of major bleeding events similar between no anticoagulant, low molecular weight heparin (LMWH) or DOAC groups.•The rate of new/recurrent VTE was similar among anticoagulant groups•Patients with a VTE had significantly worse survival than those without a VTE In patients with renal cell carcinoma (RCC) on cabozantinib, venous thromboembolism (VTE) management remains challenging due to limited safety data regarding direct oral anticoagulants (DOACs) use in conjunction with cabozantinib. We investigated the safety of cabozantinib with different anticoagulants in patients with RCC. In this retrospective multicenter study (9 sites), patients with advanced RCC were allocated into 4 groups: (1) cabozantinib without anticoagulation, cabozantinib with concomitant use of (2) DOACs, (3) low molecular weight heparin (LMWH), or (4) warfarin. The primary safety endpoint was the proportion of major bleeding events (defined per International Society on Thrombosis and Hemostasis criteria). The primary efficacy endpoint was the proportion of new/recurrent VTE while anticoagulated. Between 2016 and 2020, 298 patients with RCC received cabozantinib (no anticoagulant = 178, LMWH = 41, DOAC = 64, and warfarin = 15). Most patients had clear cell histology (78.5%) and IMDC intermediate/poor disease (78.2%). Cabozantinib was first, second, or ≥ third line in 21.8%, 31.9%, 43.3% of patients, respectively. Overall, there was no difference in major bleeding events between the no anticoagulant, LMWH, and DOAC groups (P = .088). Rate of new/recurrent VTE was similar among anticoagulant groups. Patients with a VTE had a statistically significantly worse survival than without a VTE (HR 1.48 [CI 95% 1.05-2.08, P = .02]). This real-world cohort provides first data on bleeding and thrombosis complications in patients with RCC treated with cabozantinib with or without concurrent anticoagulation. DOACs appear safe for VTE treatment for patients with RCC on cabozantinib, but optimized anticoagulation management, including individualized risk-benefit discussion, remains important in clinical practice. [Display omitted] In this retrospective multicenter study (9 sites), including 298 patients with advanced RCC, we investigated the safety of cabozantinib with different anticoagulants. DOACs appear safe for VTE treatment for patients with RCC on cabozan