4 | 2019 | hospitalpharmacyeurope.com
the treatment. The committee concluded
that standard cytarabine and daunorubicin
chemotherapy is the relevant comparator
for this appraisal.
Clinical evidence
The clinical effectiveness evidence is
relevant to NHS clinical practice in
England.
The evidence for liposomal cytarabine–
daunorubicin came from Study 301. This
was a Phase III, multicentre, open-label,
randomised trial. It included 309 adults
aged 60 to 75 years with high-risk acute
myeloid leukaemia. High-risk acute myeloid
leukaemia was defined as therapy-related
acute myeloid leukaemia, acute myeloid
leukaemia with myelodysplastic
syndrome, de novo acute
myeloid leukaemia
with myelodysplastic
syndrome-associated
karyotypic changes
and chronic
myelomonocytic
leukaemia. The
trial compared
liposomal cytarabine–
daunorubicin
(n=153) with
standard cytarabine
and daunorubicin
chemotherapy (n=156),
in a 3+7 schedule (3 days of
cytarabine then 7 days of daunorubicin).
The clinical experts confirmed that it was
reasonable to assume equivalence between
the 3+7 schedule in the trial and the 3+10
schedule normally used in the UK. They
also confirmed that, although the trial was
done in the US and Canada, the baseline
characteristics of people in the trial were
representative of people in the UK who
would be eligible for liposomal cytarabine–
daunorubicin. The clinical experts explained
that about a quarter of patients who would
be eligible for treatment in England would
be under 60 years. There was no biological
reason to expect treatment benefit to be
any different to that seen in people aged
Clinical management
Current treatment is chemotherapy.
Current treatment for therapy-related
acute myeloid leukaemia and acute
myeloid leukaemia with myelodysplasia-
related changes is intensive chemotherapy,
for people who are well enough to have
it. This usually involves a first induction
course, and two or three further courses
of standard daunorubicin and cytarabine
to treat any remaining cancer cells
(consolidation therapy). In the NHS, the
first induction course is usually given as
3 days of daunorubicin and 10 days of
cytarabine (known as DA 3+10). The clinical
experts highlighted that some younger
patients may have FLAG-Ida (fludarabine,
cytarabine, granulocyte-colony
stimulating factor and
idarubicin) chemotherapy
instead. The committee
understood that
liposomal cytarabine–
daunorubicin
is a liposomal
formulation of
standard cytarabine
and daunorubicin
chemotherapy.
This could be used
as an alternative in
clinical practice. The
committee was aware that
diagnosing some types of high-
risk acute myeloid leukaemia, particularly
de novo acute myeloid leukaemia with
myelodysplastic syndrome- associated
karyotypic changes, involves genetic
testing. In England, genetic test results
may not be available for 7 to 10 days.
The clinical experts advised that it is
becoming more common for clinicians to
wait for these test results before starting
treatment. A small number of patients
with more aggressive disease would need
to start treatment sooner. The committee
agreed that no change in practice would
be needed for most people who would
be eligible for liposomal cytarabine–
daunorubicin, if it were to recommend