65 to 70 years in the trial. The committee
concluded that the clinical-effectiveness
evidence from Study 301 was relevant to
clinical practice in England.
Liposomal cytarabine–daunorubicin
improves overall survival compared with
standard cytarabine and daunorubicin.
The primary outcome measure in Study
301 was overall survival. Treatment with
liposomal cytarabine–daunorubicin
increased median overall survival
compared with standard cytarabine
and daunorubicin, from 5.95 months
to 9.56 months (hazard ratio [HR] 0.69;
95% confidence interval [CI] 0.52 to 0.90,
p=0.005). The company also presented
results from a post-hoc analysis of
overall survival from the time of stem
cell transplant. Fifty-two people in the
liposomal cytarabine–daunorubicin group
and 39 people in the standard cytarabine
and daunorubicin group had a stem cell
transplant and were included in this
analysis. Median overall survival was 10.25
months in the standard cytarabine and
daunorubicin group and was not reached
in the liposomal cytarabine–daunorubicin
group (HR 0.46; 95% CI 0.24 to 0.89,
p=0.0046). The committee noted that there
was a plateau in the Kaplan–Meier graphs
for the liposomal cytarabine–daunorubicin
group at around 6 months after transplant,
but not for the standard cytarabine and
daunorubicin group. The clinical experts
stated that response to transplant may
differ depending on the person’s health
when they had the transplant, but that
they would expect to see a plateau from
the same time point in both groups. The
committee noted that the post-hoc analysis
included a small number of patients.
It also noted that, in the trial, the decision
to transplant was not randomised and
therefore there could be bias in the results
of the post-hoc analysis. The committee
also noted that the results presented by
the company were from a data cut in
December 2015, 3 years after the first
patient was randomised, although the
company stated that trial follow-up was
continuing for 5 years after randomisation.
Also, after 1 year, a substantial number
of patients were censored in the analysis,
which the committee agreed made the
long-term results more uncertain. In
response to consultation, the company
presented updated Kaplan–Meier graphs,
using safety data up to August 2018. It
presented graphs both for overall survival
in the full population and from the time of
stem cell transplant. The committee agreed
that the updated graphs were more reliable
because there was less censoring and there
was a plateau in both treatment groups.
The company suggested that the difference
between groups in response to transplant
was because people in the liposomal
cytarabine–daunorubicin group were in
better health before transplant or had less
residual leukaemia going into transplant,
or both. However, minimal residual disease
status before transplant was not collected
in the trial. The committee concluded that
there was some uncertainty about how
much survival was improved after stem cell
transplant, but that liposomal cytarabine–
daunorubicin improved overall survival
in the whole population compared with
standard cytarabine and daunorubicin.
Adverse effects
Liposomal cytarabine–daunorubicin is well
tolerated.
The adverse effects reported in Study 301
were broadly comparable between the
two groups. The patient expert noted that
liposomal cytarabine–daunorubicin had
been more tolerable for them than other
treatments. The clinical experts suggested
that people in the liposomal cytarabine–
daunorubicin group of Study 301 may
have taken the active treatment for longer,
leading to similar rates of adverse effects
in the two groups, rather than lower rates
in the liposomal cytarabine–daunorubicin
group as they may have expected. The
committee concluded that liposomal
cytarabine–daunorubicin was generally
well tolerated.
hospitalpharmacyeurope.com | 2019 | 5