(netupitant 100, 200 and 300mg
and 0.5mg palonosetron) provided
superior prevention of CINV
compared with oral palonosetron
following HEC; however, 300mg
NEPA was the best dose studied,
with an advantage over lower
doses for all efficacy endpoints.
The fixed combination of
netupitant and palonosetron
was well tolerated with a similar
safety profile to palonosetron,
aprepitant and ondansetron;
this was an exploratory arm
and formal comparison was
performed between this and NEPA
treatment groups. 35
The prophylactic efficacy of
NEPA against CINV remained
constant over repeated
cycles with HEC and MEC
treatment. 36–38 Notably, the dose of
dexamethasone (12mg day 1 and
8mg days 2–4) should be reduced
(as for aprepitant) with NEPA
compared with 5-HT 3 RAs alone. 39
An IV formulation of NEPA is
approved in the US and is under
evaluation by the European
Medicines Agency in the EU.
An oral formulation of the NK 1
RA rolapitant for the prevention
of delayed nausea and vomiting
associated with HEC and MEC in
adults was approved in 2017. The
efficacy of rolapitant in preventing
CINV when added to granisetron
plus dexamethasone has been
evaluated in Phase III trials in
patients receiving HEC 40 and in
patients receiving MEC or AC-based
40 | 2019 | hospitalpharmacyeurope.com
chemotherapy. 41 The addition
of rolapitant to active therapy
gave 60% improvement in the
likelihood of achieving a CR in
the delayed phase. 40
In the MEC study, rolapitant
recipients had a higher rate of CR
in the delayed phase than active-
control recipients (71 vs 62%), and
it was associated with significant
benefits in the prevention of
vomiting but not of nausea.
A prespecified analysis found that
the benefit of rolapitant on CR in
the delayed phase was maintained
irrespective of whether patients
were treated with AC.
The oral capsule formulation
of aprepitant and its water-soluble
phosphoryl prodrug, fosaprepitant,
which is administered in a single
intravenous dose, were the
first NK 1 RAs to be marketed.
Both drugs are licensed for the
prevention of acute and delayed
nausea and vomiting, associated
with MEC and HEC courses
(in combination with other
antiemetics) and prevention of
postoperative nausea and vomiting
in adults. They have particular
efficacy in delayed CINV.
Aprepitant has improved
control of CINV in combination
with a 5-HT 3 RA and
dexamethasone. Aprepitant
must be administered in
combination with a 5-HT 3 RA and
dexamethasone for three days,
regardless of the duration of the
chemotherapy cycle.