Literature Scan
New and noteworthy research from the
medical literature landscape
Is Oral Edoxaban an Alternative to Standard
Anticoagulation in Cancer-Associated VTE?
Low-molecular-weight heparin
is the standard, guideline-
recommended anticoagulation
therapy for patients with cancer
and venous thromboembolism
(VTE), but the daily subcutane-
ous injections can be burdensome.
Newer direct oral anticoagulants
could offer an easier-to-use alter-
native for these patients, without
compromising efficacy, according
to results from a non-inferiority
trial published in the New England
Journal of Medicine. Lead author
Gary E. Raskob, PhD, of the
University of Oklahoma Health
Sciences Center in Oklahoma City,
also presented these findings as a
late-breaking abstract at the 2017
American Society of Hematology
Annual Meeting.
“For the vast majority of pa-
tients with cancer-associated VTE,
treatment with oral edoxaban can
replace the injectable dalteparin,”
he said during his presentation.
“Preventing VTE recurrence and
major bleeding can allow the
oncologist to really focus on the
patient’s cancer treatment.”
The randomized, open-label
Hokusai VTE Cancer trial included
1,046 adult patients with active
cancer and acute symptomatic or
incidentally detected deep vein
thrombosis, acute symptomatic
pulmonary embolism (PE), or
incidentally detected PE involv-
ing segmental or more proximal
pulmonary arteries.
Patients were excluded if they
received more than 72 hours of
pretreatment with anticoagulants
prior to randomization, had active
bleeding or contraindication to
either study agent, or had a platelet
count less than 50,000/mL.
Participants were randomized
1:1 to receive edoxaban 60 mg
once-daily (n=522; mean age =
64.3 years; standard deviation [SD]
= 11.0 years) or dalteparin 200 IU/kg
once-daily for 30 days, followed by
dalteparin 150 IU/kg once-daily
(n=524; mean age = 53.7 years;
SD=11.7 years).
In the edoxaban cohort, 465
patients (89.1%) had solid tumors
and 56 (10.7%) had hematologic
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malignancies. In the dalteparin
cohort, 467 patients (89.1%) had
solid tumors and 55 (10.5%) had
hematologic malignancies. The
most common tumor types in
each cohort were colorectal (n=83
[15.9%] vs. n=79 [15.1%]), lung
(n=77 [14.8%] vs. n=75 [14.3%]),
and genitourinary (n=65 [12.5%]
vs. n=71 [13.5%]).
The median treatment dura-
tion was 211 days (interquartile
range [IQR] = 76-357 days) in
the edoxaban group and 184 days
(IQR=85-341 days) in the daltepa-
rin group (p=0.01). Counts of pills
and syringes indicated that 447
(85.6%) and 465 patients (88.7%),
respectively, received at least 80
percent of the prescribed treatment
prior to discontinuation.
After a minimum of nine
months of follow-up, edoxaban
was deemed non-inferior in pre-
venting the composite outcome of
recurrent VTE or major bleeding
(primary endpoint). In the edoxa-
ban group, 67 patients (12.8%)
experienced a recurrent VTE or
major bleeding, compared with 71
patients (13.5%) in the dalteparin
group (hazard ratio = 0.97; 95% CI
0.70-1.36; p=0.006).
As seen in the TABLE , secondary
outcomes, including incidence of
major bleeding and recurrent VTE
also were non-inferior between the
two treatment groups. “There was
a lower rate of recurrent VTE ob-
served with edoxaban, but that was
offset by a similar increase in risk
of major bleeding,” Dr. Raskob said,
TABLE.
adding that “major bleeding was
less severe with edoxaban, but rates
of severe bleeding were similar.”
The researchers reported no
statistically significant impact
between subgroups and treatment,
except for those with gastrointes-
tinal cancer, who were more likely
to have an increase in the risk of
bleeding while receiving edoxaban,
compared with dalteparin (p=0.02).
Adverse events (AEs) occurred
in 308 edoxaban-treated patients
(59.0%) and 286 dalteparin-treated
patients (54.6%), while serious
AEs occurred in 217 (41.6%) and
195 (37.2%) patients, respectively
(p values not reported). The most
common AEs occurring in each
cohort were:
• malignant neoplasm
progression (n=68 [13.0%] for
edoxaban vs. n=67 [12.8%] for
dalteparin)
in 116 (22.2%) and 126 (24.0%)
patients, respectively.
The study is limited by its open-
label design, although “long-term
administration of placebo injec-
tions was not considered to be
appropriate,” the authors noted. In
addition, the median duration of
the assigned treatment was shorter
with dalteparin, which may have
influenced relative efficacy.
Daiichi Sankyo provided fund-
ing for the study and was respon-
sible for the trial design, protocol,
and oversight.
The corresponding authors re-
port financial support from Daiichi
Sankyo, Bayer, Bristol-Myers Squibb,
Boeh