Clinical Outcomes of Cancer-Associated Venous Thromboembolism in Patients with Gastrointestinal or Genitourinary Cancers Treated with Direct Oral Anticoagulant Vs. Low Molecular Weight Heparin

Background Venous thromboembolism (VTE) is a common complication in patients with cancer. Direct oral anticoagulants (DOACs) have become preferred treatment strategy in many patients due to ease of use and comparable efficacy to low molecular weight heparin (LMWH). However, higher rates of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) seen in clinical trials led guidelines to caution against DOAC use in high-risk bleeding populations, such as those with gastrointestinal (GI) and genitourinary (GU) cancer. Retrospective data regarding use of DOACs in GI cancer has been analyzed with varying results, and there is a paucity of data regarding bleeding risk in those with GU cancer. This study aimed to describe bleeding events and recurrent VTE in patients with GI and GU cancers treated with DOAC vs. LMWH. Methods We conducted a retrospective review of patients with GI or GU cancer who had an index VTE event between January 2015 and February 2021 seen at the Clevland Clinic's ambulatory cancer-associated thrombosis (CAT) clinic. Starting in 2017, the CAT clinic has followed a clinical guideline which suggests DOAC treatment for patients with a low risk of bleeding and no drug interactions. There is shared decision making regarding the increased risk of bleeding in GI/GU patients, and LMWH is preferred in these patients. Contraindication to DOACs use included patients with recent active bleeding, GFR <30 ml/min, severe hepatic impairment, platelet count <50,000, and/or expected malabsorption at the level of stomach or small bowel. In the absence of complications, patients are advised to continue anticoagulation as long as the cancer is active or still being treated. Data captured included patient demographics, type of VTE (deep vein thrombosis (DVT), pulmonary embolism (PE) or both), cancer treatment, and clinical outcomes which included VTE recurrence, MB or CRNMB as defined by the International Society on Thrombosis and Hemostasis. The last date of chart review in these patients was 6/20/2024 and date of last follow-up and/or death was captured for all patients. For statistical analysis, patients were matched by age and cancer stage. For both total and matched patients, association of patient characteristics with treatment group (DOAC or LMWH) was evaluated via univariate analyses, using Fisher's exact test for categorical variables and Kruskal- Wallis test for continuous variables. Time to first bleeding event was analyzed using log rank test. Results The study population was comprised 94 patients with gastrointestinal (n=48, 51.1%) and genitourinary cancers (n=46, 48.9%) who had an index VTE event and were started on either a DOAC (n=38, 40.4%) or LMWH (n=56, 59.6%). Of all patients, 67 (71.3%) were male and the median age was 62 years. DVT was the most common VTE (n=70, 74.5%) followed by PE (n=14, 14.9%), and both DVT&PE (n=10, 10.6%). 10 patients (10.64%) had a prior history of VTE. Colon cancer (n=19, 20.2%) was the most frequent cancer type followed by prostate (n=16, 17.0%), esophageal (n=13, 13.8%), bladder (n=13, 13.8%), renal (n=12, 12.8%), rectum (n=10, 10.6%), testes (n=5, 5.3%), stomach (n=3, 3.2%), and anus and anal canal (n=3, 3.2%). Most patients had active cancer (n=90; 95.7%), stage 4 disease (n=64, 68.1%), and were on cancer-directed treatment (n=63, 67.0%). Of 38 patients treated with DOAC, 9 patients (23.7%) had a bleeding event (MB=2, 5.3%; CRNMB=7, 18.4%) and 4 patients (10.5%) had a recurrent VTE. Of 56 patients treated with LMWH, 17 patients (30.4%) had a bleeding event (MB=6, 10.7%; CRNMB=11, 19.6%) and 5 patients (8.9%) had a recurrent VTE. There was no difference in the rate of MB or CRNMB between patients who received DOAC or LMWH (p=0.67 for all patients, p=1.0 for matched patients). Similarly, there was no difference in the rate of VTE recurrence between patients who received DOAC or LMWH (p=1.0 for all patients and for matched patients). The median time to first bleeding event in matched patients was 23 months with a 5-year bleeding free survival rate of 38%. Discussion In this study, gastrointestinal or genitourinary cancer patients treated for VTE had similar bleeding and VTE recurrence rates when treated with a DOAC or LMWH. Shared decision making with patients regarding use of DOACs in this patient population remains important. Future research should prospectively assess the safety profile of DOACs in the management VTE among patients with GI and GU malignancies.