Study Finds New Predictors of Recurring Cancer-Specific Thrombosis

Alok Khorana, MD

A new analysis of results from the CATCH study reveals two major clinical predictors for recurrence of venous thromboembolism (VTE) in cancer patients that may help in the identification of patients at increased risk. These include venous compression by the tumor and a diagnosis of hepatobiliary cancer.

Study results were presented as a poster at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Even with adequate anticoagulation therapy, cancer patients with acute VTE have a six- to seven-times higher risk of another VTE event compared with patients who have no previous VTE. Until now, reliable clinical predictors or biomarkers for recurrence of VTE have been lacking, making identification of those at increased risk a challenge.

“Anticoagulation is effective but it increases the risk of bleeding, which is almost as frequent as clotting [in cancer patients],” explains Alok Khorana, MD, of Cleveland Clinic’s Department of Hematology and Medical Oncology. “The current standard of care is daily self-injection of low-molecular weight heparin (LMWH), which can be challenging for patients.” Being able to select a subgroup of patients at risk would enable clinicians to deliver more customized care.

“These findings suggest that treatment of cancer-associated thrombosis can be individualized based on risk of recurrence, with more intensive strategies reserved for high-risk patients,” says Dr. Khorana, a senior author on the study.

A step closer to individualized treatment

The CATCH trial was a large, international, multicenter, randomized, phase III trial that compared the use of tinzaparin (LMWH) and warfarin in cancer patients with VTE. It was the largest study to date of the treatment of cancer-related thrombosis and included 900 patients from 165 sites across five continents. Patients with active cancer of varied types and acute, symptomatic proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were enrolled.

The results showed that LMWH lowers the risk of recurrent VTE compared with warfarin over a period of six months without sacrificing safety or increasing the risk of bleeding events. The next piece of the puzzle was to identify those at a higher risk of recurrent VTE, which would enable clinicians to tailor treatments appropriately, thus improving patient outcomes and lowering costs.

“The ability to have more individualized approaches to treatment has not previously been appreciated,” says Dr. Khorana. “I can see this evolving into a care pathway where low-risk patients are treated in a certain way (shorter duration of anticoagulation, less intense strategies), and higher-risk patients with a more intensive approach.”

The search for reliable predictors

During the six-month study involving 900 randomized patients, 6.9 percent of those treated with tinzaparin had recurrent VTE compared with 10 percent of patients treated with warfarin (hazard ratio 0.65; 95% CI 0.41– 1.03; p = 0.07). The authors looked at several clinical variables, including presence of metastases, chemotherapy, recent hospitalization, radiation therapy, ECOG performance status, and venous compression from a tumor mass or adenopathy.

“The most important aspect of the new analysis is the finding of a subgroup that is at higher risk of recurrence, which suggests more intense [anticoagulation treatment] strategies could be reserved for this subgroup,” says Dr. Khorana. “Venous compression is fairly prevalent in gynecologic tumors, while hepatobiliary cancer is relatively rare, occurring in 5 percent or so of patients.”

Highlights from the results include:

• The risk factors associated with recurrent VTE are tumor venous compression (HR 2.96; 95% CI 1.8–4.86; p < 0.001) and diagnosis of hepatobiliary cancer (HR 2.91; 95% CI 1.2– 7.02; p = 0.018).
• Ottawa score did not predict the risk of VTE recurrence in this study; the recurrent VTE rates were 3.4, 9.7 and 8.2 percent in low-, intermediate-, and high-risk groups, respectively.

Improving on Ottawa score

The Ottawa score is a recently developed risk assessment model (RAM) for VTE recurrence that includes four independent clinical predictors (sex, primary tumor site, stage, and prior VTE) and a score sum ranging between -3 and 3 score points. Patients with a score ≤ 0 have low risk (≤ 4.5 percent) and patients with a score > 1 have a high risk (≥ 19 percent) for VTE recurrence. The validation of this RAM has been controversial.

“Our result suggests that Ottawa score is an incomplete risk assessment tool. These findings need to be validated, and care path approaches to different risk populations need to be studied appropriately,” says Dr. Khorana. “We are currently studying biomarker prediction in 800 patients from this trial and I believe this will further refine identification of high-risk patients.”

Follow Dr. Khorana on Twitter @aakonc.