Treatment Of Cancer-associated Thrombosis Research Articles

Factor XI inhibitors: a new option for the prevention and treatment of cancer-associated thrombosis

Venous thromboembolism (VTE) is a relatively common complication in cancer patients with potentially dire consequences. Anticoagulants are the mainstay of treatment of cancer-associated VTE. The anticoagulants most often used are low-molecular-weight heparin (LMWH) and direct oral factor (F) Xa inhibitors, which include apixaban, edoxaban, and rivaroxaban. Most guidelines recommend primary VTE prophylaxis with LMWH, apixaban, or rivaroxaban after abdominal or pelvic cancer surgery, or in high-risk ambulatory cancer patients. Both oral FXa inhibitors and LMWH have limitations. LMWH requires daily subcutaneous injections, and because of its renal clearance, its use may be problematic in patients with severe kidney disease. The risk of bleeding with oral FXa inhibitors may be higher than with LMWH in patients with intraluminal gastrointestinal or genitourinary cancers. Other problems with oral FXa inhibitors include potential drug-drug interactions and dosing issues in patients with thrombocytopenia or severe kidney or liver disease. Therefore, there remains a need for convenient and safer anticoagulants for VTE treatment in cancer patients. FXI has emerged as a potentially safer target for anticoagulants than FXa because FXI is essential for thrombosis, but mostly dispensable for hemostasis. This review summarizes the currently available therapeutic options for cancer-associated VTE, highlights knowledge gaps, and discusses the potential of FXI inhibitors to address key unmet clinical needs in this vulnerable patient population.

Venous thromboembolism treatment in patients with cancer: reflections on an evolving landscape

Cancer is a leading cause of morbidity and mortality worldwide. It is also one of the strongest risk factors for venous thromboembolism (VTE), reported in approximately 20% of all cases of VTE diagnosed. The thrombotic effect of cancer and its treatments, however, is highly variable among patients and changes over the course of their cancer. Anticoagulant therapy remains the cornerstone of VTE treatment, but it is associated with a substantial rate of VTE recurrence and the potential for serious bleeding. The risk of bleeding in patients with cancer is also dependent on the cancer type and its treatments, often revealing underlying tumor invasion of mucosal or parenchymal tissues, and treatment complications such as thrombocytopenia or coagulopathy. Over the past few decades, efforts to improve the efficacy and safety of anticoagulant therapy for the treatment and prevention of cancer-associated thromboembolism have resulted in changes in the standard of practice. This evolution has been made possible largely through the development of new anticoagulants. This review will reflect on the major advances in the treatment of cancer-associated thrombosis and offer insights on how to address unmet needs in this field.

Cancer-associated thrombosis in hematologic malignancies.

Patients with hematologic malignancies are often complicated not only by severe bleeding due to thrombocytopenia and disseminated intravascular coagulation but also by thromboembolic events, just like in patients with solid cancers, and these events can negatively impact patient outcomes. Nevertheless, the prevention and treatment of cancer-associated thrombosis (CAT) in hematologic malignancies has not been adequately investigated due to the limited size, heterogeneity, and unique pathophysiology of the patient population. This article summarizes the current understanding, risk factors, prediction models, and optimal prevention and treatment strategies of CAT in hematologic malignancies on a disease-by-disease basis, including acute leukemia, lymphoma, myeloma, and myeloproliferative neoplasms. Specific considerations of novel molecular targeted therapeutics introduced in recent years, such as immunomodulatory drugs and tyrosine kinase inhibitors, are also discussed based on the latest clinical trials.

Overall Survival of Warfarin Compared to LMWH/Doacs in Cancer-Associated Venous Thromboembolism: VA Cohort Study

Background: Warfarin has been shown in pre-clinical models to have anti-neoplastic activity. In a population-based study using the SEER-Medicare Linked Database warfarin was associated with improved survival compared to low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) in the treatment of cancer-associated thrombosis (CAT). To assess whether the observed survival advantage is consistent in other large cohorts, we performed a matched cohort study utilizing the Veterans Affairs (VA) database. The VA is a large, integrated health care system with comprehensive data for their patients at the individual level, which provides the optimal observational cohort to confirm the novel hypothesis warfarin confers a mortality benefit over LMWH. Method: Using the retrospective data from the VA health care system from 2000-2021, we identified patients with CAT who were > 18 years, had available prescription data for anticoagulation within 30 days of venous thromboembolism (VTE), and survived > 14 days after the index VTE event. Patients were excluded if they had prior diagnosis of VTE or had any anticoagulation prescription prior to the first coded VTE event. The primary outcome was overall survival (OS). Patients were matched 1:1 using nearest neighbor matching on the propensity score. The matching variables included cancer site, cancer stage, date of cancer diagnosis, date of VTE diagnosis, age at VTE diagnosis, gender, race, BMI, Elixhauser-based weighted comorbidity score, and rurality of residential status. Cox proportional-hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals. Log-rank test was utilized to estimate the p-value. Subgroup analyses were performed in the largest groups of cancer available in the data set including prostate cancer, lung cancer, gastrointestinal cancer (excluding hepatobiliary cancer), and malignant hematologic neoplasms (including myeloid malignancy, lymphoid malignancy, and multiple myeloma). Finally subgroup analysis was also performed on localized cancer and metastatic disease based on AJCC stage grouping. Result: There were a total of 20,078 patients that met the inclusion and exclusion criteria without missing data. The warfarin cohort consistent of 8383 patients while non-warfarin cohort comprised 11696 patients. Among the non-warfarin cohort, 54% of the patients were prescribed LMWH exclusively and 38% of the patients were prescribed DOAC exclusively within 30days of the VTE diagnosis. The most common malignancies in the cohort included prostate (29.4%), lung (20.9%), gastrointestinal (15.7%) and hematologic malignancies (10.3%). Of patients with solid tumors, 22% had metastatic cancer. Among the VTE events, 33.3% were acute lower extremity deep vein thrombosis, 48.4% were acute pulmonary embolism, and 18.3% were acute upper extremity deep vein thrombosis. After propensity score matching, 8,383 patients were included in the warfarin arm and 8,383 patients in the non-warfarin arm. The median age at VTE diagnosis of the matched cohort was 69 [IQR 63 - 75] and the majority of the patients (96.7%) were male. Warfarin was associated with a significant improvement in OS compared to non-vitamin K antagonists (median OS, 1204 days [95% CI, 1137-1276 days] vs 703 days [95% CI, 665-747 days]; HR 0.79 [95% CI 0.76 - 0.82]; p-value <2x10 -16) (Figure1). The difference was also preserved in gastrointestinal malignancy (HR 0.8 v95% CI 0.73-0.87), lung cancer (HR 0.8, 95% CI 0.79-0.92) and prostate cancer (HR 0.71, 95% CI 0.65-0.77). The survival advantage was preserved in patients with metastatic (HR 0.86, 95% CI 0.78-0.83) and localized cancer (HR 0.80, 95% CI 0.76-0.84) (Figure 2). Conclusion and Relevance: In a population level propensity matched study, warfarin for the treatment of CAT was associated with significantly improved survival over non-vitamin K antagonist anticoagulation in CAT. These provocative finding confirm the previous observation in SEER-Medicare database and have important implications on patient care and health care costs. Further investigation into the biological basis of these findings could potentially lead to biomarker and drug discovery for cancer therapies and prognostication.

EE504 Cost-Effectiveness of a Novel Treatment for Cancer-Associated Thrombosis (CAT): Results from an Early Economic Analysis

Direct oral anticoagulants and low-molecular weight heparins have demonstrated to be effective in preventing or treating cancer-associated thrombosis (CAT), but they also interfere with hemostasis leading to an increased risk of bleeding and decreased adherence. As a result, many patients with CAT do not receive adequate treatment in terms of dose and/or duration, which can lead to less favorable outcomes. This early economic analysis explored the potential cost-effectiveness of a hypothetical new therapy for the treatment of CAT from a UK perspective.

Pharmacokinetic drug-drug interactions with direct anticoagulants in the management of cancer-associated thrombosis.

Drug-drug interactions (DDIs) are common in cancer management and complicate the choice of anticoagulation in cancer-associated thrombosis. Cancer confers an increased risk of thrombotic events. Also, more bleeding events are observed in those who receive anticoagulation compared to those without cancer. In the treatment of cancer-associated thrombosis, direct oral anticoagulants (DOACs) have been found to be at least as effective as low-molecular weight heparins, which became the standard of care after several trials demonstrated superiority over vitamin K antagonists. Non-inferiority compared to low-molecular weight heparins has been shown for rivaroxaban, edoxaban and apixaban with a signal of fewer recurrent thrombotic events, albeit with an increase in bleeding events. Yet, potentially major pharmacokinetic drug-drug interactions have been identified as a reason to withhold DOACs and to rather choose an alternative. Practical guidance on what constitutes a major pharmacokinetic interaction and/or how to deal with these interactions in clinical practice is limited. Hence, here we have provided a framework to allow clinicians to better deal with pharmacokinetic drug-drug interactions between DOACs and cancer therapies in the management of cancer-associated thrombosis. In this review we have discussed the current literature, how the pharmacokinetic profile links to the label information on DDI, and have provided a practical proposal, applied to a clinical case.

An Update in Anticoagulant Therapy for Patients with Cancer-Associated Venous Thromboembolism.

This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion. Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient.

Practical Considerations for the Management of Cancer-Associated Venous Thromboembolism: A Guide for the General Oncology Practitioner.

Cancer-associated venous thromboembolism is a devastating complication of cancer and is associated with significant morbidity and mortality. The cornerstone of cancer-associated venous thromboembolism treatment is anticoagulation, and in recent years, there have been notable randomized clinical trials that have revealed insights into the efficacy and safety of direct oral anticoagulants and low-molecular-weight heparin in the treatment of cancer-associated thrombosis. Deciding on the ideal anticoagulation treatment plan for a patient with a cancer-associated thrombosis is a complex task that requires an understanding of clinical trial data, society guidelines, and, most importantly, consideration of many cancer-related, treatment-related, and patient-related factors. This article summarizes important factors to consider when deciding on anticoagulation therapy for a patient with cancer-associated thrombosis.

EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer.

In cancer patients, thrombocytopenia can result from bone marrow infiltration or from anticancer medications and represents an important limitation for the use of antithrombotic treatments, including anticoagulant, antiplatelet, and fibrinolytic agents. These drugs are often required for prevention or treatment of cancer-associated thrombosis or for cardioembolic prevention in atrial fibrillation in an increasingly older cancer population. Data indicate that cancer remains an independent risk factor for thrombosis even in case of thrombocytopenia, since mild-to-moderate thrombocytopenia does not protect against arterial or venous thrombosis. In addition, cancer patients are at increased risk of antithrombotic drug-associated bleeding, further complicated by thrombocytopenia and acquired hemostatic defects. Furthermore, some anticancer treatments are associated with increased thrombotic risk and may generate interactions affecting the effectiveness or safety of antithrombotic drugs. In this complex scenario, the European Hematology Association in collaboration with the European Society of Cardiology has produced this scientific document to provide a clinical practice guideline to help clinicians in the management of patients with cancer and thrombocytopenia. The Guidelines focus on adult patients with active cancer and a clear indication for anticoagulation, single or dual antiplatelet therapy, their combination, or reperfusion therapy, who have concurrent thrombocytopenia because of either malignancy or anticancer medications. The level of evidence and the strength of the recommendations were discussed according to a Delphi procedure and graded according to the Oxford Centre for Evidence-Based Medicine.

A modern approach to the treatment of cancer-associated venous thromboembolic complications: a lecture

Cancer-associated venous thromboembolic complications are one of the main topical problems in the system of practical healthcare. Having overlapping pathogenetic mechanisms of development, thromboembolic complications accompany the oncological process and often act as its manifesting sign. Treatment of onco-associated venous thromboembolic complications is not an easy task, which is determined by the multiplicity of the pathogenetic mechanisms of hemostatic system disorders in the cohort of patients under consideration, who are threatened both in terms of the development of total PE and fatal bleeding. In addition to the features of the treatment phases, their duration, an important point in the treatment of cancer-associated thrombosis is a limited list of recommended drugs, as well as the permitted dosage regimens. The article analyzes the results of research aimed at studying the effectiveness of apixaban in the treatment of cancer-associated thromboembolic complications. Now the gold standard for the treatment of venous thromboembolic complications is dalteparin. However, low compliance in the use of dalteparin leads to premature termination of treatment or the patient's independent transition to alternative drugs. The appearance of direct oral anticoagulants has significantly changed the treatment paradigm in this morbid group of patients, while leaving a number of unresolved issues.

Direct Oral Anticoagulants in the Management of Cancer-Associated Venous Thromboembolism: A Comprehensive Review

Venous thromboembolism (VTE) is reportedly the second common cause of death among cancer patients. Management of VTE with low molecular weight heparins (LMWH) and Vitamin K antagonists (VKA) is associated with significant clinical challenges that led to the emergence of direct oral anticoagulants (DOAC) as an alternative for the management of cancer-associated thrombosis (CAT). The objective of this review is to provide an updated review of the completed and upcoming randomized controlled clinical trials (RCT) comparing the safety and efficacy of DOAC versus LMWH in the management of CAT in adults. A comprehensive literature survey was conducted till 7th January 2021 to review the completed randomized controlled clinical trials (RCT) comparing the safety and efficacy of DOAC versus LMWH in the management of CAT in adults. In order to search for upcoming trials, the Cochrane library and clinicaltrials.org databases were surveyed until the same period. The author found four completed RCT of DOAC in the management of CAT. Apart from these, there were another four RCT that are either ongoing or are yet to publish data. DOAC were reported to be noninferior to LMWH in the treatment of cancer-associated thrombosis in cancer patients with low bleeding risk and without gastrointestinal or gastrourinary cancers. Among patients with gastrointestinal or gastrourinary cancers and VTE, LMWH are preferred.

The importance of consensus statements on the prevention and treatment of cancer-associated thrombosis

Venous thromboembolism (VTE) is a common complication among patients with cancer. The 6-month risk of VTE complication for cancer patients is 12-fold higher and as much as 23-fold higher in those receiving chemotherapy or targeted therapy when compared to patients without cancer [1]. Furthermore, the 12-month cumulative incidence for VTE has increased three-fold over the past two decades in this patient population [1]. Hence, cancer-associated thrombosis (CAT) is a frequent complication that most clinicians caring for patients with cancer must routinely manage.

Consensus on prevention and treatment of cancer-associated thrombosis (CAT) in controversial clinical situations with low levels of evidence

BackgroundCancer patients suffer high risk of venous thromboembolism (VTE). Cancer-associated VTE (CAT) causes hospitalization, morbidity, delayed cancer treatment, and mortality; therefore, exceptional CAT prevention and management are imperative. MethodsThis review offers practical recommendations and treatment algorithms for eight complex, clinically relevant situations posing great uncertainty regarding management and requiring an urgent decision: VTE prophylaxis in ambulatory cancer patients with pancreatic pancreas (1) or lung cancer with molecular alterations (2); optimal management of VTE during antineoplastic treatment with antiangiogenics (3) or chemotherapy (4); protracted VTE treatment, determinants; (5) drugs used (6), and optimal VTE management in situations of high bleeding risk (7) or recurrent VTE (8). ResultsWith the evidence available, primary thromboprophylaxis in patients with lung cancer harbouring ALK/ROS1 translocations or pancreatic cancer receiving ambulatory chemotherapy must be appraised. If antiangiogenic therapy can yield a clear benefit and the patient recovers from a grade 3 thrombotic event, it can be cautiously re-introduced in selected cases, provided that the person agrees to assume the risk after being duly informed. Anticoagulation maintenance beyond 6 months is recommended in individuals with metastatic tumours, on active treatment, or at high risk for recurrent VTE without bleeding risk. In such cases, LMWH and DOACs are safe, being mindful that the latter could entail a higher risk of bleeding; consequently, they should be used judiciously in more haemorrhagic tumours, such as gastrointestinal cancers. In cases of recurrent VTE, the presence of active cancer, infra-therapeutic dose, and anticoagulant treatment failure must be ruled out. In individuals with platelet counts of 25,000–50,000 and VTE liable to recur who need anticoagulation, full-dose LMWH and transfusion support can be contemplated to reach values of > 50,000. In CAT unlikely to recur, decreasing the LMWH dose by 25–50% is recommended. Renal impairment associated with thrombosis must be treated with LMWHs; there is no need to adjust the dose in patients with CrCl > 30; with CrCl = 15–30, dose adjustment is advised, and suspended when CrCl is < 15. ConclusionWe provide useful advice for complex, clinically relevant situations that clinicians treating CAT must face devoid of any unequivocal, strong, evidence-based recommendations.

Bleeding Outcomes in Patients with Gastrointestinal Malignancies Treated with Distally Absorbed Versus Proximally Absorbed Direct Oral Anticoagulants

Introduction: Randomized trials comparing direct oral anticoagulants (DOACs) to low molecular weight heparin demonstrated higher rates of bleeding associated with DOACs, especially in patients with gastrointestinal (GI) malignancies. DOACs differ in location of absorption with apixaban predominately absorbed in the distal small bowel and proximal colon and edoxaban, rivaroxaban and dabigatran absorbed in the proximal GI tract (e.g. stomach and proximal small intestine). No comparative data is available for the DOACs in treatment of cancer-associated thrombosis (CAT). Given the differences in location of absorption, we aimed to assess the association of bleeding in patients with GI malignancy and CAT on apixaban versus those treated with proximally absorbed DOACs (dabigatran, edoxaban, or rivaroxaban).Methods: Using a nationwide cohort of Veterans, we identified patients with active GI malignancy between 2012 and 2018. Using a previously validated algorithm (91% positive predictive value), we identified patients with newly diagnosed VTE. A VTE was considered to occur in the setting of active cancer if the diagnosis occurred (1) within 3 months before cancer diagnosis, (2) within 6 months after cancer diagnosis, or (3) any time after diagnosis of metastatic cancer. We limited the cohort to patients who received at least a 30-day prescription for anticoagulant therapy with apixaban, dabigatran, edoxaban or rivaroxaban. Patients with a prescription for any anticoagulant therapy within 6 months before VTE diagnosis were excluded. We retrospectively followed patients to 30-days after the last DOAC prescription or to death, whichever came first. The primary outcome of interest was clinically significant bleeding while on DOAC therapy. We defined clinically significant bleeding as the presence of an ICD-9 or ICD-10 code for bleeding in any position for an inpatient admission with 3 exceptions: microscopic hematuria, bleeding related to major trauma and metromenorrhgia. We assessed the association between DOAC use and bleeding as a time-to-event outcome while adjusting for the competing risk of non-bleeding related death through the methods of Fine and Gray.Results: Between 2012 and 2018, a total of 215 patients with GI malignancies received a DOAC for treatment of CAT. Eighty-six patients received apixaban and the remaining 129 received a proximally absorbed DOAC with the majority receiving rivaroxaban (80%). Baseline demographics by anticoagulant therapy are listed in Table 1. None of the clinical variables assessed were significantly different between patients on apixaban versus a proximally absorbed DOAC, including variables associated with risk of anticoagulant-related bleeding.Of the 215 patients included, 73% were diagnosed with a distal GI malignancy (colon or lower). During the follow-up period, 43 of 215 patients (20%) experienced a clinically significant bleeding event, 22.1% of patients on apixaban and 18.6% of patients on a proximally absorbed DOAC. Of the 43 bleeding events, 30 were bleeding from the GI tract. In patients on apixaban versus a proximally absorbed DOAC, there was no significant difference in the risk of clinically significant bleeding (hazard ratio (HR) 1.24; 95% confidence interval (CI): 0.67 - 2.21). Similarly, there was no significant difference in the risk of bleeding from the GI tract in patients on apixaban versus a proximally absorbed DOAC (HR 0.90; 95% CI: 0.43 - 1.89).Conclusion: In this study of 215 patients with GI malignancy, we found no significant difference in the risk of bleeding between patients treated with apixaban versus those treated with a proximally absorbed DOAC. The rate of clinically significant bleeding was high (20%) while on DOAC therapy. There is a continued need for future prospective studies evaluating antithrombotic therapy in patients with GI malignancies and CAT. [Display omitted] DisclosuresSanfilippo: AstraZeneca: Research Funding; Atellas Pharma Global: Research Funding. Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding.

How to Choose An Appropriate Anticoagulant for Cancer-Associated Thrombosis.

Venous thromboembolic disease can be a fatal complication of cancer. Despite advances in prevention, thousands of patients require treatment of cancer-associated thrombosis (CAT) each year. Guidelines have advocated low-molecular-weight heparin (LMWH) as the preferred anticoagulant for CAT for years, based on clinical trial data showing LMWH to be associated with a lower risk of recurrent thrombosis when compared with vitamin K antagonists. However, the potentially painful, subcutaneously administered LMWH injections can be expensive, and clinical practice has not been consistent with guideline recommendations. Recently, studies have compared LMWH to the direct oral anticoagulants (DOACs) for the management of CAT. Based on promising trial results outlined in this review, DOACs are now preferred anticoagulants for CAT occurring in patients without gastric or gastroesophageal lesions. For patients with gastrointestinal cancers, who may be at higher risk of hemorrhage with the DOACs, LMWH remains the anticoagulant of choice. Applying the latest data from this rapidly evolving field to care for diverse patient groups can be challenging. This article provides an evidence-based review of outpatient anticoagulant selection for lower-extremity deep vein thrombosis or pulmonary embolism in the setting of cancer, and takes into account special populations with cancer.

Patient education program at the forefront of cancer-associated thrombosis care.

Treatment of cancer-associated thrombosis (CAT) requires specific approaches, although it is well codified in most cases. Current national and international (International Initiative on Cancer and Thrombosis, ITAC) Clinical Practice Guidelines (CPG) recommend the use of low-molecular-weight heparin (LMWH) over 6 months as first treatment option, and anticoagulation should be maintained thereafter as long as cancer is active. Since compliance improves when patients understand their disease and related treatments, we created a dedicated patient education program (PEP) for CAT, aiming to improve quality of care. Retrospective analysis of all patients who voluntarily joined the PEP for CAT from 2014 to 2020. In total, 182 cancer patients (median age, 64.9 years) were included, 53.3% with metastatic disease. A total of 528 PEP sessions (median, 3 per patient) were delivered. After PEP completion, the rate of self-injections or those performed at home by a relative had increased from 49.1% to 59.8% (P=0.05). Quality of life had improved significantly (P=0.025) and 90.0% of patients reported adhering to anticoagulant therapy. Implementation of a structured and personalized PEP for CAT is feasible, allowing to improve cancer patient empowerment, adherence to CAT treatment and quality of life. The Groupe francophone et cancer (GFTC) members aim at facilitating access to CAT-PEP for both patients and caregivers and use of the multi-language ITAC-CPG mobile app (free access: www.itaccme.com) to improve the care and quality of life of patients with CAT.

499P The safety and efficacy of edoxaban for the cancer-associated asymptomatic venous thromboembolism in Japanese gastrointestinal cancer patients receiving chemotherapy (ExCAVE study)

Initial administration of heparin is recommended when using edoxaban, a direct oral anticoagulant that has been shown to be non-inferior to low molecular weight heparin in the treatment of cancer-associated thrombosis (CAT), but it is often not practiced in actual clinical practice due to its complexity. The aim of this study was to assess the safety and efficacy of edoxaban alone treatment without initial heparin usage for asymptomatic CAT in patients with gastrointestinal cancer (GIC) who are reported to be at high risk of bleeding.

Management of Cancer-Associated Thrombosis: Unmet Needs and Future Perspectives.

Patients with cancer are at a high risk of symptomatic venous thromboembolism (VTE), which is a common cause of morbidity and mortality in this patient population. Increased risk of recurrent VTE and bleeding complications are two major challenges associated with therapeutic anticoagulation in these patients. Long-term therapy with low-molecular-weight heparins (LMWHs) has been the standard of care for the treatment of cancer-associated VTE given its favorable risk–benefit ratio in comparison with vitamin K antagonists. Direct oral anticoagulants (DOACs), which offer the convenience of oral administration and have a rapid onset of action, have recently emerged as a new treatment option for patients with cancer-associated thrombosis (CT). Randomized clinical trial data with head-to-head comparisons between DOACs and LMWHs showed that overall, DOACs have a similar efficacy profile but a higher risk of bleeding was observed in some of these studies. This review aims to identify unmet needs in the treatment of CT. We discuss important considerations for clinicians tailoring anticoagulation (1) drug–drug interactions, (2) risk of bleeding (e.g., gastrointestinal bleeding), (3) thrombocytopenia, hematological malignancies, (4) metastatic or primary brain tumors, and (5) renal impairment. Additional research is warranted in several clinical scenarios to help clinicians on the best therapeutic approach.

Risk Assessment Models for Thrombosis and Anticoagulant-Related Bleeding in Ambulatory Cancer Patients.

Cancer patients have a high risk of developing venous thromboembolism and arterial thrombosis, along with an increased risk of anticoagulant-related bleeding with primary and secondary prophylaxis of cancer-associated thrombosis. Decisions on initiation, dosing, and duration of anticoagulant therapy for prevention and treatment of cancer-associated thrombosis are challenging, as clinicians have to balance patients' individual risk of (recurrent) thrombosis against the risk of bleeding complications. For this purpose, several dedicated risk assessment models for venous thromboembolism in cancer patients have been suggested. However, most of these scores perform poorly and have received limited to no validation. For bleeding and arterial thrombosis, no risk scores have been developed specifically for cancer patients, and treatment decisions remain based on clinical gestalt and rough and unstructured estimation of the risks. The aims of this review are to summarize the characteristics and performance of risk assessment scores for (recurrent) venous thromboembolism and discuss available data on risk assessment for bleeding and arterial thrombosis in the cancer population. This summary can help clinicians in daily practice to make a balanced decision when considering the use of risk assessment models for cancer-associated venous thromboembolism. Future research attempts should aim at improving risk assessment for arterial thrombosis and anticoagulant-related bleeding in cancer patients.

The Net Clinical Benefit of Rivaroxaban Compared to Low-Molecular-Weight Heparin in the Treatment of Cancer-Associated Thrombosis: Systematic Review and Meta-Analysis.

Cancer-associated thrombosis (CAT) carries significant morbidity and mortality. Low-molecular-weight heparin (LMWH) remains the standard of care, with recent systematic studies suggesting the efficacy and safety of rivaroxaban in the treatment of CAT. Uncertainty, however, remains regarding rivaroxaban efficacy and safety in real-world settings. We performed a systematic review and meta-analysis of studies comparing rivaroxaban to LMWH. We searched PubMed, MEDLINE, and EMBASE. The primary outcome was the net clinical benefit (NCB), while rates of major bleeding (MB), venous thromboembolism (VTE), clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality events were secondary outcomes. Seventeen studies were included in the final analysis. Rivaroxaban had a better NCB (relative risk [RR] = 0.82; 95% CI = 0.75-0.89, Q = 10.51, I 2 = 0%), less VTE events (RR = 0.73, 95% CI = 0.65-0.82, Q = 6.76, I 2 = 0%), and lower all-cause mortality (RR = 0.72, 95% CI = 0.57-0.91, Q = 32.8, I 2 = 79%) compared to LMWH. Additionally, comparable MB events (RR = 1.07, 95% CI = 0.85-1.33, Q = 16.9, I 2 = 11%). However, CRNMB events were higher in the rivaroxaban group (RR = 2.02, 95% CI = 1.46-2.80, Q = 9.9, I 2 = 19%). Additional analyses demonstrated consistency of results. Our review encompassing data from randomized and real-world data suggested rivaroxaban superiority compared to LMWH in terms of a better NCB, fewer VTE events, lower all-cause mortality, and comparable MB risk while carrying a higher risk of CRNMB. These findings support the use of rivaroxaban in the treatment of CAT. Additionally, it warrants a sizable randomized controlled study testing the superiority of rivaroxaban versus LMWH formulation and ascertaining bleeding outcomes according to cancer type and site.