Evaluating the Need for Anticoagulation Beyond 6 Months for Patients with Cancer-Associated Venous Thromboembolism (VTE): A Retrospect of Real Life (EXTEND study - updated results)

Background

Last year, we presented at the 56^th ASH meeting (abstract 4245) preliminary results of the EXTEND study. We would like to present the complete results of this retrospective cohort study conducted in London, Canada.

Current thrombosis and oncology guidelines recommend low molecular weight heparin (LMWH) for a minimum of 6 months for treatment of cancer-associated thrombosis (CAT). After the first 6 months,  if malignancy is still active or anti-cancer therapy is ongoing, guidelines recommend continuation of anticoagulation, even though no guidance with respect to what best treatment option is indicated. This paucity of data led our group to evaluate what has been the preferred clinical approach for anticoagulation continuation or cessation for patients with CAT beyond the first 6 months of anticoagulation.

Methods

We retrospectively collected data from adult clinical patients with CAT who received anticoagulation treatment with LMWH or warfarin for at least 6 months (from January 2007 to December 2013). 

Inclusion criteria: 18 years old or older; any type of active cancer; any cancer stage or treatment; use of LMWH or warfarin during the first 6 months of anticoagulation for an acute CAT.

Follow up period started at 6 months of anticoagulation and finished at 12 months (total of 6 months of study follow-up), or  ended at time of a recurrent VTE; or death; or last follow up in clinic.

Exclusion Criteria: anticoagulation for less than 6 months of; or recurrent VTE within the first 6 months of anticoagulation; or bone marrow transplantation. 

  The primary outcome measure is VTE recurrence rate and its correlation with anticoagulation strategy after the first 6 months of anticoagulation.

Results

 Of 417 potential patients, 289 fulfilled our inclusion criteria. 284 (98%) received LMWH and 4 (2%) warfarin during the first 6 months of treatment. There were 146 males (50.5%), median age was 66 (24 - 73). Hematological cancers were 52 (18%), and solid tumors were 143 (50.5%): the most common being lung (41/14%) and colon (55/ 19%). One hundred eighty six (64%) patients had stage III or IV malignancy. At CAT diagnosis, there were 144 DVTs, 116 PEs and 22 had both. There were 45 (32.6%) incidental PEs. At 6 months of anticoagulant therapy, 73 (25%) patients discontinued therapy and the remaining 216 patients were as follows: 139 (48%) continued on full dose LMWH, 18 (6.2%) on prophylactic LMWH, 66 (22.8%) were switched to warfarin, 3 (1%) to rivaroxaban (Table).

Between 6 and 12 months of follow up, 77 patients were considered to be in remission of their cancer but 51 (66.2%) still continued on anticoagulation. In total, 18 of 289 (6.2%) patients had a recurrent VTE. Only 2 had discontinued anticoagulation. There was no significant difference in the relative risk of recurrence in patients with ongoing active malignancy or considered to be in remission [0.79 (95%CI 0.316 – 1.99); p= 0.625]. Of the 45 patients with incidental PE at first CAT, 4 (10%) presented with a recurrent VTE during our follow up period. All patients were on full dose LMWH.

 The only potential independent predictor for VTE recurrence was having a hematological or lung cancer [OR= 3.62 (95% CI (1.356 – 9.67) p=0.0102].Details of the univariate analysis in the table. The multivariate analysis included tumor site, discontinuation of anticoagulation or full LMWH but only tumor site was statistically significant.

Conclusion

 Patients with CAT appear to have an ongoing high risk for recurrent VTE even though this risk appears to be lower than in the first 6 months of anticoagulants which historically ranges around 9 and 17%. In our study we were not able to accurately identify potential predictors of recurrence. However, we were able to demonstrate that patients with incidental PE are indeed at a significant recurrence risk and as such, should receive standard anticoagulation treatment. In addition, it appears that patients with hematological or lung cancer are at higher risk of recurrence.

Table- Univariate analysis VTE recurrence risk during the 6 to 12 months after CAT diagnosis

Predictor	OR (95% CI)	p-value
Lung or Heme cancer Full LMWH Proph LMWH Oral anticoag. No anticoag. Stage  Residual VTE Gender  Age Complete remission	3.6 (1.35 – 9.67) 1.8 (0.66-4.66) 0.8 (0.11-7.00) 0.9 (0.31-3.00) 2.8 (0.64-12.65) 1.1 (0.28-3.91) 1.5 (0.41-5.75) 0.8 (0.31-2.10) 1.6 (0.57-4.29) 1.4 ( 0.51- 3.89)	0.0102 0.259 0.903 0.949 0.171 0.722 0.507 0.659 0.384 0.508