In a large retrospective analysis, Cleveland Clinic researchers uncovered a substantial lack of adherence to prescribed guidelines in the treatment of venous thromboembolism (VTE) in cancer patients.
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Patients with cancer have a six to 12 times higher chance of developing a VTE (either deep vein thrombosis or pulmonary embolism), and it is the second leading cause of death in this population. Cancers associated with very high VTE risk are stomach, pancreas and brain, while high VTE risk is known for lung, lymphoma, gynecologic, bladder, testicular and renal cancers. The standard of care in the treatment of cancer-associated thrombosis is low-molecular-weight heparins (LMWH).
“However, there are challenges to using LMWHs,” notes Alok Khorana, MD, of Cleveland Clinic’s Department of Hematology and Medical Oncology. Dr. Khorana is lead author for the study, which was presented at the 57th American Society of Hematology Annual Meeting & Exposition in December in Orlando, Fla.
“First of all, LMWHs are daily self-injections, and cancer patients are already burdened with many demands on their time as a result of their treatments. Adding a daily injection to that is challenging,” Dr. Khorana says. “Moreover, anticoagulant therapies are long-term treatments with a minimum duration of three to six months, and are often needed for life in cancer patients.In addition, patients’ cost for injectables can be higher than for oral agents based on their insurance plan.
As a result of these factors, many if not most patients with cancer-associated thrombosis don’t actually receive the standard-of-care LMWH, Dr. Khorana says. This study clarifies the actual numbers.
Uncovering numbers through insurance data analysis
The study analyzed medical and pharmacy claims from the large Humana database. Patients who experienced a first VTE after a first cancer diagnosis between Jan. 1, 2013, and Dec. 31, 2014 – a total of 2,941 cases – were included. Based on the first anticoagulant agent received, patients were classified into one of four cohorts: LMWH, LMWH/warfarin, warfarin and rivaroxaban. Therapy termination was set as a time gap of more than 60 days after supposed finishing of the last known allotted prescription, and therapy duration was assessed for 12 months.
“In this study, we looked at real-world prescribing patterns,” says Dr. Khorana. “We looked at the proportion of patients receiving different types of treatment, and how long the patients remained on those specific treatments.”
Of the total patients receiving anticoagulant therapy, 97 percent received anticoagulation with either LMWH (n=735; 25 percent), LMWH/warfarin (n=550; 18.7 percent), warfarin (n=853; 29 percent), or rivaroxaban (n=709; 24.1 percent). At six months, 37, 60, 62 and 61 percent of patients in each cohort remained on their respective therapies. At 12 months, 21, 37, 34 and 36 percent, respectively, remained on their initial therapy.
Of the patients given LMWH, 22.9 percent switched to another anticoagulation treatment, compared with 8.9, 7.3 and 4.7 percent for those started on LMWH/warfarin, warfarin and rivaroxaban, respectively.
Highlights from the study include:
• Only 25 percent of patients received LMWH as their first anticoagulant prescription.
• Patients taking LMWH remained on the treatment just slightly over three months (median 3.29 months), while those given the other three treatments lasted between seven and eight months (7.76, 8.12 and 7.92 months for LMWH/warfarin, warfarin and rivaroxaban, respectively).
• Patients who received the other three treatments also were much more likely to stick to their initial therapy, unlike those given LMWH, who were more likely to switch.
“It turns out based on our analysis of this very large data set that, in fact, LMWH is not the most widely used anticoagulant, and that patients are frequently prescribed alternate agents,” says Dr. Khorana. “If patients are prescribed LMWH, they don’t appear to continue therapy as long as they do if they are prescribed an oral agent.”
Cost-of-care and preference realities win out over guidelines, but oral therapies need more study
The bottom line is that treatment of cancer-associated thrombosis remains highly variable, which is likely driven by physician and patient preference and cost of care.
“I think this is a reflection of how difficult it is to translate guideline recommendations into real-life practice, and how this sort of financial toxicity is very real for cancer patients,” says Dr. Khorana.
Even though the new oral anticoagulants (NOACs) are cheaper and more convenient, the downside is primarily the lack of evidence to support their use in cancer patients. In other patient populations, NOACs have been shown to be non-inferior to warfarin, which is known to be inferior to LMWH. And because they are oral agents, there is concern about how well they are absorbed in cancer patients.
“We need to determine whether the newer oral agents are safe and feasible to use in cancer patient populations,” Dr. Khorana says. “These studies are ongoing and we will have those results in the near future.”