A Prospective Study of Apixaban for Central Venous Catheter Associated Upper Extremity Deep Vein Thrombosis in Cancer Patients: Catheter 3

Introduction Upper extremity deep vein thrombosis (UEDVT) represents up to 10% of cases of venous thromboembolism (VTE) and is frequently associated with central venous catheter (CVC) placement in patients receiving chemotherapy for cancer. UEDVT may be treated with low molecular weight heparin (LMWH) either as monotherapy or subsequently transitioned to warfarin as we have previously shown (Kovacs 2007). In the Catheter 2 Study (Davies 2018) we showed that Rivaroxaban had efficacy but in the 70 patients that were included there were 6 major bleeds (8.6%) and 1 death due to pulmonary embolism (PE). Given these findings we decided to evaluate the safety and efficacy of Apixaban in the treatment of UEDVT secondary to CVC in patients with cancer.

Methods We conducted a prospective cohort study at 3 centres in Canada between May 2017 and December 2021. We enrolled patients ≥18 years of age with active malignancy and symptomatic proximal UEDVT (axillary or more proximal) with or without PE, associated with a CVC. Exclusion criteria included dialysis catheters, active bleeding, platelet count <75 x 10⁹/L, creatinine clearance <30 mL/min, PE with hemodynamic instability, inability to infuse through the catheter after a trial of intraluminal thrombolytic therapy (tissue plasminogen activator, tPa), patients with acute leukemia, patients with multiple myeloma awaiting bone marrow transplant within 3 months, thrombosis involving the brachial, basilic or cephalic veins only, treatment for >7 days with other anticoagulants, need for dual antiplatelet therapy (recent stent), or concomitant use of P-glycoprotein and CYP3A4 inhibitors. The primary objective was to estimate catheter survival at 3 months (defined as a catheter that did not develop infusion failure not responding to 2 mg of tPa). Secondary outcomes included recurrence of DVT, PE, major bleeding, clinically relevant non-major bleeding (CRNMB) and death. All events were independently adjudicated. Due to the fact that in the Catheter 2 Study most bleeds occurred while taking 15 mg bid of Rivaroxaban, for this study, patients were treated with dalteparin, 200 IU/kg x 7days followed by Apixaban 5 mg po bid to complete 12 weeks. tPa for management of blocked lines was allowed. Patients were followed clinically for 12 weeks to assess for clinical events including recurrent symptomatic VTE, major bleeding and CRNMB.

Results We included 70 patients (41, 59% women) with a mean age of 62 years. DVTs were diagnosed by ultrasound and 2 patients (3%) also had PE at baseline. The most common veins involved were axillary (n=53, 76%) and subclavian (n=52, 74%), followed by the brachial, internal jugular, brachiocephalic and external jugular. Peripherally inserted central catheters (PICC) were the most common (n=56, 80%), followed by port-a-cath lines (n=14, 20%). Types of active malignancy included breast (n=22, 31%), colon (n=12, 17%), colorectal (n=7, 10%), lung (n=4, 6%), bladder (n=3, 4%), pancreatic (n=3, 4%) and other (n=19, 27%).

Catheter survival was 57% at 12 weeks with no catheters removed due to thrombosis and all catheters were functional until removal or end of study. Reasons for CVC removal prior to the end of the study included end of therapeutic need (n=21), infection (n=3), accidentally fell out (n=3), patient preference (n=1), and death (n=2). One patient (1.4%) had a recurrent DVT in the same arm during the 3-month follow-up period. The 2 patient deaths were both due to underlying cancer. There were 7 bleeding events in 6 patients, 3 major (2.9%) and 4 CRNMB (5.7%). (1 patient had 2 major bleeds).

Discussion In this study, Apixaban showed promise in treating CVC-associated UEDVT in cancer patients, resulting in high preserved CVC function.

Wells:Bayer HealthCare: Honoraria. Carrier:Servier: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Leo Pharma: Honoraria, Research Funding.