SAN FRANCISCO—Low-molecular-weight heparin (LMWH) should replace warfarin as thromboprophylaxis in cancer patients, according to a speaker at the 2014 ASH Annual Meeting.

Results of the phase 3 CATCH trial showed that long-term treatment with the LMWH tinzaparin was associated with a 35% lower risk of recurrent venous thromboembolism (VTE) when compared to warfarin, although the difference between the treatment arms was not statistically significant.

Patients who received tinzaparin did have a significantly lower risk of symptomatic deep vein thrombosis (DVT) and clinically relevant, non-major bleeding.

However, there was no difference between the treatment arms with regard to major bleeding or overall mortality.

Agnes Y.Y. Lee, MD, of the University of British Columbia and Vancouver Coastal Health in British Columbia, Canada, presented these results at ASH as LBA-2.*

“CATCH is the largest randomized trial studying treatment of cancer-associated thrombosis,” she said. “It provides confirmatory data for improved efficacy of low-molecular-weight heparin over warfarin.”

The trial included 900 cancer patients from 164 centers around the world. The mean patient age was 59 (range, 18-89), and 59% were female. The most common cancers were gynecologic, colorectal, upper gastrointestinal, and lung.

Patients were stratified by geographic region, tumor characteristics, and history of VTE. They were randomized to receive tinzaparin at 175 IU/kg once daily for 6 months (n=449) or initial tinzaparin at 175 IU/kg once daily for 5 to 10 days overlapped and followed by dose-adjusted warfarin for 6 months (n=451).

In all, 416 patients completed treatment with tinzaparin, and 401 completed warfarin treatment. The patients were followed up to 6 months or death, whichever came first.

Efficacy data

The primary efficacy outcome was recurrent VTE, which included symptomatic DVT and/or pulmonary embolism (PE), incidental proximal DVT and/or PE, and fatal PE.

The rate of recurrent VTE was 7.2% in the tinzaparin arm and 10.5% in the warfarin arm (hazard ratio [HR]=0.65, P=0.07). This represents a 35% reduction in recurrent VTE with the LMWH.

In the per-protocol analysis, the rates of recurrent VTE were 8.3% and 12.7%, respectively (HR=0.62), which translates to a 38% reduction in recurrent VTE with tinzaparin.

“Pre-specified efficacy analyses further showed that tinzaparin significantly reduced symptomatic, recurrent DVT by 52%,” Dr Lee noted. “There were very few symptomatic PEs, equal numbers of fatal PEs occurred in each arm, and there were only 2 incidental thrombotic events, both in the warfarin arm.”

Symptomatic, non-fatal DVT occurred in 12 patients (2.7%) in the tinzaparin arm and 24 (5.3%) in the warfarin arm (HR=0.48, P=0.04). Symptomatic, non-fatal PE occurred in 3 patients (0.7%) and 2 patients (0.4%), respectively. And fatal PE occurred in 17 patients (3.8%) in each arm (HR=0.96).

“We were clearly disappointed that our primary efficacy outcome did not achieve statistical significance,” Dr Lee said. “But our sample size was based on an estimated recurrent [VTE] rate of 12.6% in the warfarin group, and we only saw a 10% [sic] recurrence. So, basically, our study was slightly underpowered to achieve statistical significance.”

“I think that, given the symptomatic DVT results, as well as the per-protocol analysis, in additon to all the previous data on low-molecular-weight heparin, this is still very strong confirmatory data that low-molecular-weight heparin is more effective than warfarin therapy in treating cancer patients with thrombosis.”

Safety and mortality

The primary safety endpoint was major bleeding, which occurred in 2.9% of patients in the tinzaparin arm and 2.6% in the warfarin arm (HR=0.89).

The rate of clinically relevant, non-major bleeding was 11.1% and 16.2%, respectively (HR=0.69, P=0.03).

“Tinzaparin reduced the rate of clinically relevant, non-major bleeding by 31%,” Dr Lee noted.

On the other hand, there was no significant difference between the arms with regard to 180-day overall mortality, which was 34.2% in the tinzaparin arm and 32.3% in the warfarin arm (HR=1.08).

This research was sponsored by LEO Pharma, the company developing tinzaparin (Innohep).

*Information in the abstract differs from that presented at the meeting.

LMWH should replace warfarin, doc says