International Trial Supports Alternative to Warfarin For Cancer-Specific Thrombosis

Results from Phase III CATCH trial add data to what was already a consensus-driven treatment option: low-molecular weight heparin.

Patients who have cancer and acute venous thromboembolism (VTE) have an increased risk of recurrent VTE in the future. In fact, as many as one in five patients with cancer will have an occurrence of a cancer-specific thrombosis, notes Alok Khorana, MD, of Cleveland Clinic’s Department of Hematology and Oncology.

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“Knowing how best to treat VTE has been a challenge in the past,” Dr. Khorana says. The standard anticoagulant therapy at one point was warfarin, but data from a 2003 study introduced a newer and potentially more effective option: low-molecular weight heparin (LMWH).

The challenge: “In real-world practice, only about 20 to 30 percent of patients are getting low-molecular weight heparin as a treatment,” Dr. Khorana says. “It’s not clear why, although we do speculate on some reasons.”

Dr. Khorana is senior author of a large, international, multicenter randomized trial designed to provide more clear clinical guidance for the use of LMWH in treating patients with VTE. It is the largest study to date on the treatment of cancer-related thrombosis. The results, presented at the 56th American Society of Hematology Annual Meeting and Exposition, show that LMWH can lower the risk of recurrent VTE compared with warfarin, without sacrificing safety or increasing the risk of bleeding events.

Moving From Consensus to Data

Dr. Khorana offers some possible reasons why LMWH has failed to take hold as a preferred treatment. LMWH has existed as a consensus-based treatment option for a few years, but the field may crave more data before moving it into practice.

For one thing, physicians in an era of evidence-based medicine want confirmation studies with large numbers of patients. In addition, the original study on LMWH was specific to North America; questions persisted as to whether treatment outcomes would differ in certain populations, such as those in Asia.

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“This study was written to capture a much larger population — and to be conducted in various centers around the world,” he says. “We want to rely on hard evidence that compares appropriate treatments. We also wanted to know, could we safely reduce the risk of clotting events without increasing the risk of bleeding events.

With these goals in mind, the “CATCH” study included 900 patients from 165 sites across five continents. This Phase III trial included patients with active cancer of varied types and acute, symptomatic proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE).

Researchers randomized treatment groups and delivered 175 IU/kg of tinzaparin, a type of LMWH, to 449 patients once daily for six months. They treated 451 patients with dose-adjusted warfarin for the same timeframe. They then measured for efficacy, determined by time to recurrent VTE — including symptomatic DVT and/or PE, incidental proximal DVT and/or PE, and fatal PE. For safety, the researchers measured incidence of major bleeding.

Highlights from the results include the following:

  • During the trial’s six months, 6.9 percent of the patients in the LMWH arm experienced recurrent VTE, compared with 10 percent in the warfarin arm (hazard ration 0.65 [95 percent Cl 0.41–1.03;P=0.07]).
  • There was no difference in the incidence of major bleeding events in the two study arms. However, only 11 percent of patents in the LMWH arm experienced clinically relevant non-major bleeding such as nosebleeds and bruising, compared with 16 percent for the warfarin arm. (P=0.03)
  • Additionally, there was no difference in mortality between the two study arms.

Moreover, Dr. Khorana notes that looking at the composite of all the types of thrombotic events studied in the trial, patients in the LMWH arm experience roughly a 35 percent reduction in events. This was true regardless of geography, as well.

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“The hope is that these data clearly support the recommendation from guidelines that the best treatment for cancer-associated thrombosis is six months of low-molecular weight heparin,” he says.

Dr. Khorana points to additional benefits, as well — including those for patients, payers and the healthcare system as a whole.

“The cost of treatment can be very substantial,” he notes. “A cancer patient with VTE has average inpatient cost of roughly $21,000 if they have a blood clot versus $7,000 without such an incident. Getting the right treatment guidelines in place can bring that cost down.”