Here are several more abstracts selected from the proceedings of the 2015 American Society of Hematology (ASH) Annual Meeting and Exposition, focusing on the topic of anticoagulation and the cancer patient. For other selected abstracts from this conference, see the December 25, 2015, and the February 10, 2016, issues of The ASCO Post. For full details of these study abstracts, visit https://ash.confex.com/ash/2015/webprogram/start.html.
Abstract 427: Dalteparin thromboprophylaxis in ambulatory cancer patients who are at high risk for venous thromboembolism: A randomized trial: dalteparin vs no thromboprophylaxis1
Question Asked: What is the benefit of dalteparin (Fragmin; 5,000 U daily subcutaneously for 12 weeks) prophylaxis in ambulatory cancer patients at high risk (defined as Khorana score ≥ 3) for venous thromboembolism?
Abstract Conclusion: Venous thromboembolism occurred in 12% (6 of 50) of patients on the dalteparin arm and 21% (10 of 48) patients on the control arm (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.23–1.89; absolute risk reduction, 9%; relative risk reduction, 42%; number needed to treat to benefit 1 patient, 12). Major bleeding was similar (n = 1) in each arm, but clinically relevant bleeding was higher in the dalteparin arm (n = 7 vs 1 in the control arm; HR = 7.0, 95% CI = 1.2–131.6). There was no difference in overall survival. The most common primary sites of cancer were the pancreas, gastroesophageal junction, lungs, and blood (lymphoma).
Thromboprophylaxis is associated with a nonsignificant reduced risk of venous thromboembolism. Of the 117 enrolled patients, 10 patients were not randomized due to the presence of venous thromboembolism on initial screening (n = 10, 8.5%); these data suggest that consideration should be given to screening high-risk (Khorana score ≥ 3) patients in clinical practice prior to starting systemic therapy.
Abstract 431: Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease in a highly selected group of cancer patients. Outcome analysis of first 100 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), who have been treated for at least 6 months or otherwise reached the study endpoint2
Question Asked: What are the safety and efficiency data of rivaroxaban (Xarelto), and how does it compare with the current standard of anticoagulation therapy with low–molecular-weight heparin, specifically dalteparin, in a highly preselected group of patients with cancer-associated thrombosis?
Abstract Conclusion: At 6 months, new or recurrent venous thromboembolism was 4.3% (95% CI = 0.1–8.4%), major bleeding was 1.1% (95% CI = 0–3.1%), and clinically relevant nonmajor bleeding leading to rivaroxaban discontinuation was 7.9% (95% CI = 2.1–13.3%). In this analysis of the first 100 patients who entered into the MSKCC quality improvement initiative program, the rates of major bleeding and new or recurrent venous thromboembolism compared favorably with those in two published studies with low–molecular-weight heparin for the treatment of cancer-associated thrombosis.
In the CLOT3 and DALTECAN4 studies, the 6-month rates of new or recurrent venous thromboembolism were approximately 9%, and the rates of major bleeding were 6% and 9.5%, respectively. The final analysis awaits the completion of 6 months of follow-up on 200 patients, anticipated to be completed shortly.
The low rates of major bleeding in this study likely are influenced by the exclusion of patients with active gastrointestinal or genitourinary cancer, who would be expected to have a high bleeding risk with rivaroxaban, a direct oral anticoagulant. Further, the investigators anticipated reduced drug clearance in older (> 75 years) adults and reduced the dose of rivaroxaban in these individuals. This particular approach does not appear to be associated with loss in efficacy and helped maintain a low rate of major bleeding. A randomized trial is the optimal approach to establish noninferiority or superiority of rivaroxaban to low–molecular-weight heparin (current standard) for cancer-associated thrombosis.
Abstract 432: A single-center retrospective analysis evaluating and comparing rivaroxaban with dalteparin for the treatment of cancer-associated thrombosis5
Question Asked: Is rivaroxaban effective and safe compared with dalteparin for the treatment of cancer-associated thrombosis?
Abstract Conclusion: No significant differences in the efficacy and safety profile were demonstrated between rivaroxaban and dalteparin.
Abstract 2319: A single-center retrospective analysis evaluating the effectiveness and safety of rivaroxaban in the treatment of cancer-associated thrombosis6
Question Asked: Is rivaroxaban effective and safe when compared with dalteparin in the treatment of cancer-associated thrombosis?
Abstract Conclusion: Only four patients (4.3%) experienced recurrent venous thromboembolism with rivaroxaban therapy. Ten patients (10.8%) experienced major bleeding, and the median time to major bleeding was 4.4 months (interquartile range, 2.4–11.6 months). These data suggest that rivaroxaban may be a safe and acceptable alternative to dalteparin in the treatment and secondary prevention of cancer-associated thrombosis.
Abstract 430: Switching to warfarin after 6 months of low–molecular-weight heparin for cancer-associated thrombosis7
Question Asked: Following completion (6 months) of therapy with low–molecular-weight heparin, can patients be switched to warfarin?
Abstract Conclusion: In this study, the data set of those who enrolled in a computerized registry of patients with venous thromboembolism was evaluated. For patients who completed 6 months of low–molecular-weight heparin therapy, switching to warfarin is not associated with an increased incidence of recurrent venous thromboembolism, major bleeding, or total bleeding when compared with continuing therapy with a low–molecular-weight heparin.
Abstract 626: Current practice patterns and patient persistence on anticoagulant treatments of cancer-associated thrombosis8
Question Asked: What are the current real-world “treatment patterns” regarding anticoagulation therapy for cancer-associated thrombosis?
Abstract Conclusion: The real-world analysis based on this study showed that despite guidelines recommendation of low–molecular-weight heparin as standard of care for cancer-associated thrombosis, warfarin and rivaroxaban are nearly equally utilized as low–molecular-weight heparin for this purpose. Therapy with low–molecular-weight heparin was associated with significantly lower persistence rates and shorter duration of recommended treatment when compared with warfarin or rivaroxaban therapy. More patients switched from low–molecular-weight heparin to other anticoagulants than started on warfarin or rivaroxaban treatment for cancer-associated thrombosis.
Abstract 428: Outcomes of low–molecular-weight heparin treatment of venous thromboembolism in patients with primary and metastatic brain tumors9
Question Asked: What are the efficacy and safety of low–molecular-weight heparin treatment for newly diagnosed cancer-associated thrombosis in patients with primary and metastatic brain tumors at a tertiary-care center in Canada?
Abstract Conclusion: Recurrent venous thromboembolism, major bleeding, and clinically relevant bleeding were not significantly different in patients with cancer-associated thrombosis in the setting of primary or metastatic brain tumor compared with controls. However, intracranial bleeding occurred more frequently in patients with brain tumors. Subgroup analysis revealed that the incidence of intracranial bleeding in patients with primary brain tumors was higher than those with metastatic brain tumors, but it did not reach statistical significance (6.0% vs 3.5%, P = .008). ■
Disclosure: Dr. Abutalib reported no potential conflicts of interest.
References
1. Khorana AA, Francis CW, Kuderer N, et al: Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: A randomized trial. 2015 ASH Annual Meeting, Abstract 427. Presented December 4, 2015.
2. Mantha S, Miao Y, Sarasohn D, et al: Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: A quality improvement initiative. 2015 ASH Annual Meeting, Abstract 431. Presented December 4, 2015.
3. Lee AY, Levine MN, Baker RI, et al: Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349:146-153, 2003.
4. Francis CW, Kessler CM, Goldhaber SZ, et al: Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: The DALTECAN Study. J Thromb Haemost 13:1028-1035, 2015.
5. Chaudhury A, Balakrishnan A, Thai C, et al: Evaluation of rivaroxaban and dalteparin in cancer associated thrombosis. 2015 ASH Annual Meeting, Abstract 432. Presented December 4, 2015.
6. Win KZ, Wilson N, Stenehjem DD, et al: Effectiveness and safety of rivaroxaban in treatment of venous thromboembolism in cancer patients. 2015 ASH Annual Meeting, Abstract 2319. Presented December 4, 2015.
7. Chai-Adisaksopha C, Iorio A, Crowther MA, et al: Switching to warfarin after 6-month completion of anticoagulant treatment for cancer-associated thrombosis. 2015 ASH Annual Meeting, Abstract 430. Presented December 4, 2015.
8. Khorana AA, McCrae K, Milentijevic D, et al: Current practice patterns and patient persistence on anticoagulant treatments for cancer-associated thrombosis. 2015 ASH Annual Meeting, Abstract 626. Presented December 4, 2015.
9. Chai-Adisaksopha C, ALKindi SY, Cheah M, et al: Outcomes of low-molecular-weight heparin treatment for venous thromboembolism in patients with primary and metastatic brain tumors. 2015 ASH Annual Meeting, Abstract 428. Presented December 4, 2015.
