BACKGROUND: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis.
METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode.
RESULTS: Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P=0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24).
CONCLUSIONS: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb-Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865 .).
A perfectly good study but with predictable results.
Although the results are not particularly surprising, it is important to rely on evidence-based results rather than gestalt or anecdotal evidence. This study also puts to rest the suggestions from some that more bleeding vs stronger prophylaxis than was found would be expected.
I think this is new and interesting, but I'm not in heme-oncology. In the absence of an improvement in overall survival, I'm unsure it should change practice. Most VTE is not fatal, and one would end up giving anticoagulation to about 10% of the group rather than 100%.
This addresses a significant problem and provides a signal that this intervention may be valuable; however, it has significant limitation that limits generalization.
Oncologists are already using oral factor X inhibitors in selected patients with established thromboembolic events at the cost of higher risk of bleeding (both major and minor), so the results of this study are not surprising. Treatment was for only 6 months and we know that risk for thromboembolic events continues over time in this patient population. Should patients undergo prophylaxis on a continuous basis? This would certainly increase the risk for bleeding. 90% of the patients receiving placebo did not sustain an event. We need more information on risks and benefits with longer use before this practice is adopted. Physicians need to familiarize themselves with the Khorana scoring system, but a more predictive tool is required.
A well conducted trial that addresses an important facet of patient management. The results of this trial are known through oral presentations. It is good to have the full data published.
As a Uro Oncologist, I find this article is important in staking the claim of Eliquis (Apixaban) as prophylaxis. Patients with prostate cancer who have either undergone extensive pelvic lymphadenectomy or have bulky locally advanced disease, do present with DVT and it was a little odd that this cohort did not have too many patients with prostate cancer. Patients who undergo radical cystectomy for muscle-invasive bladder cancer are another large group of patients at risk for DVT and Apixaban would be useful in them; currently, we use LMWH in the post-op period as prophylaxis.
The authors emphasize that clots are averted by treatment, but bleeding was also increased and there was no difference in mortality (and NS increase in mortality in the treatment arm). No cost-benefit analysis. Should not change treatment at this time.
At last some evidence to support using a DOAC for cancer patients and showing safety as well as efficacy.
Multiple cancers not just lung cancer and not in proportion to incidence. I presume these are all metastatic and not locally advanced. A small minority may be at risk. Are the potential risks and costs worth it? These issues are more directed to medical than radiation oncologists.