The risk for venous thromboembolism (VTE) in cancer patients receiving chemotherapy is considerably greater in clinical practice than in recent major clinical trials, according to a "real world" study of a healthcare claims database.
"The VTE rates reported in our study are much higher than those observed in randomized clinical trials," write the authors, led by Gary Lyman, MD, from the Duke University School of Medicine and Duke Cancer Institute in Durham, North Carolina.
Three months after the start of chemotherapy, the VTE rate in the cohort of patients with solid tumors was 7.3%. That rose to 13.5% at 12 months, they report.
The study was published online November 8 in The Oncologist.
The findings are not wholly surprising, said Alok Khorana, MD, the Hardis Chair in Oncology Research at the Taussig Cancer Institute of the Cleveland Clinic, who was not involved in the study. "The study validates what clinicians have been reporting anecdotally," he told Medscape Medical News in an interview.
The researchers retrospectively reviewed the IMPACT claims database, which consists of case information from managed care plans in the United States. They identified more than 27,000 patients who initiated chemotherapy from 2005 to 2008 for cancer of the lung, pancreas, stomach, colon/rectum, bladder, or ovary.
One of the strengths of this study is that the IMPACT database includes both hospitalized patients and outpatients, Dr. Khorana noted.
Dr. Lyman and colleagues defined a VTE case as any patient with at least 1 VTE claim (based on ICD-9-CM code). The highest incidence of VTE was found in patients with pancreatic (11.6%), lung (8.5%), and stomach (8.3%) cancers.
At 3.5 months, 65.9% of the VTE cases were deep vein thrombosis (DVT), 17.6% were pulmonary embolism (PE), and 16.5% were both. That pattern of distribution was similar at 12 months.
When 2 "more stringent" definitions of a VTE were used, the DVT and PE rates were lower but nonetheless "similar."
The 7.3% VTE rate 3 months after chemotherapy initiation is higher than rates in the placebo groups of the Prophylaxis of Thromboembolism During Chemotherapy (PROTECHT) trial (3.9%) and the SAVE-ONCO study (3.4%). Both were randomized controlled trials of prophylactic low-molecular-weight heparin (LMWH) in chemotherapy patients at risk for VTE.
The higher rates found in this study "could be the result of the selection of lower-risk patients for inclusion in clinical trials," write Dr. Lyman and colleagues.
There are 2 factors that are generally driving the increasing rate of VTEs in cancer patients on chemotherapy in clinical practice.
"Since the late 1990s, more blood clots are being discovered incidentally," Dr. Khorana said. This phenomenon coincides with improvements in the scanning technology used routinely in cancer staging, he explained.
The second factor is that newer chemotherapy and targeted therapy regimens for cancer are more thrombogenic than older treatments, said Dr. Khorana. The 2 most outstanding examples are bevacizumab (Avastin, Genentech), which is commonly used in colorectal, lung, and ovarian cancer, and thalidomide (Thalomid, Celgene), which is used in myeloma, he said.
The upshot of this study is that "patients considered at high risk for VTE should be considered for thromboprophylaxis, after assessing the balance of potential benefits and harms," the authors state.
Which patients are most likely to develop a VTE?
Metastatic disease was present in a "notably higher proportion" of patients who developed VTE at 3.5 months than of those who did not (62% vs 50%), the authors report.
But they also note that, overall, the demographics and comorbidities of patients who developed VTE after the start of chemotherapy were "similar" to those of patients in who did not. In short, there was not a lot of differentiation.
Dr. Khorana urged clinicians to talk to patients about the risk for VTE related to chemotherapy and cancer, and the warning signs and symptoms. Oncologists are good at talking about hair loss, neutropenia, and other adverse effects of treatment, he said, "but we are not as good at talking about venous thromboembolism."
Telling cancer patients that they are at increased risk for VTE is "crucial," according to the American Society of Clinical Oncology clinical practice guidelines on VTE prophylaxis and treatment in patients with cancer, which were recently updated. Dr. Lyman was cochair of the guidelines panel.
Bleeding Complications Also Analyzed
The authors also reviewed major bleeding in chemotherapy patients, and found that rates were higher in patients who developed VTE than in those who did not. The rate of major bleeding complications was "high" in patients in who developed VTE at 3.5 months (11.0%) and at 12 months (19.8%).
The authors point out that the use of preventive anticoagulant treatment in the cohort was very low, at approximately 5% or 6%. However, they do not believe that the bleeding rates in patients with VTEs were a consequence of anticoagulant use.
"Although there is concern regarding the risk for bleeding with anticoagulants, studies of VTE prophylaxis with low-molecular-weight heparins, and most recently with the ultra-LMWH semuloparin, have not shown a significant increase in major bleeding rates compared with placebo," they write.
The writing of the study was supported by Sanofi. Some of the study authors are employees of Sanofi or have financial ties to the company.
Oncologist. Published online November 8, 2013. Abstract
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Cite this: VTEs With Chemo 'Much Higher' in Real World Than in Trials - Medscape - Nov 12, 2013.