A Pill Instead of a Needle for Cancer-Associated Venous Thromboembolism? YES!

Not a clinic goes by where I don’t hear, “don’t you have a pill I can take instead of a needle?” from a patient with cancer-associated venous thromboembolism (VTE). The 2017 ASH Annual Meeting brings hope that we are finally able to say “yes” to some of these patients.

Current guidelines recommend that patients with cancer-associated VTE be treated with low-molecular-weight heparin (LMWH).^1,2  At initial presentation, the compliance rate is usually high; it becomes harder to convince patients to continue injections as their VTE symptoms improve. Furthermore, the need to continue protection for months to years in patients who are maintained on chemotherapy makes the injections more burdensome.

Oral direct anticoagulants are an attractive alternative; however, less than 9 percent of those enrolled in the randomized controlled trials for these agents had cancer.³  For this reason, practitioners have greatly anticipated the results from the Hokusai VTE-Cancer Study — a multinational, open-label, blinded outcome assessment, randomized controlled trial — announced at the 2017 ASH Annual Meeting.⁴  This 1,050-patient study was designed to determine if LMWH for five days followed by edoxaban 60 mg daily (30 mg daily for creatinine clearance 30-50 mL/hr, body weight <60 kg, or receiving P-glycoprotein inhibitor) was noninferior to dalteparin (200 IU/kg daily for one month followed by 150 IU/kg daily) for treatment of VTE.

The primary outcome measure, a composite of recurrent symptomatic VTE and major bleeding at 12 months, occurred in 67 (12.8%) of 522 patients in the edoxaban arm compared with 71 (13.5%) of 524 in the dalteparin arm (hazard ratio 0.97; 95% CI, 0.70 to 1.36; p=0.0056).⁵  The risk differences for recurrent VTE and major bleeding were –3.8 percent (95% CI, –7.1 to –0.4) and 3.1 percent (95% CI, 0.5% to 5.7%), respectively. Consequently, the investigators concluded that edoxaban is just as effective and safe as dalteparin for treatment of cancer-associated VTE.

There are additional results that will be of interest once the full manuscript for this study is published. One example is the rate and sites of nonmajor clinically relevant bleeding (NMCRB). While the rate of major bleeding is the primary safety outcome measure, NMCRB episodes occur more frequently and often lead to interruptions in anticoagulant therapy, which increase the risk of recurrence. Second, details on the chemotherapeutic agents used by trial participants will be useful. Some inhibitors of P-glycoprotein were excluded from the trial entirely (e.g., protease inhibitors), while others were permitted after randomization. Lastly, the frequency of bleeding with edoxaban during periods of chemotherapy-induced thrombocytopenia will be of great interest. Dose adjustments were protocolized for dalteparin in this high-risk setting, whereas adjustments of edoxaban were left to the discretion of the investigator. In summary, we need reassurance that the patients treated with edoxaban fit the wide spectrum of cancer patients currently treated with LMWH outside of clinical trials.

In general, the results of this study make it the biggest game-changer for venous thrombosis in 2017. It is nice to know that we will finally be able to say “yes” to some patients with cancer-associated VTE who want a break from needles.