1. This study examined the use of aprepitant to treat breakthrough chemotherapy-induced nausea and vomiting (CINV) in patients who were refractory to other antiemetics. The study analyzed retrospective data from 98 metastatic melanoma patients undergoing immunotherapy who received aprepitant after a cyclophosphamide preparative regimen. 2. The primary objective was to compare the number of emetic episodes in the 48 hours before and after aprepitant administration. The secondary objective was to compare use of PRN (as needed) antiemetics in the 48 hours before and after. 3. The results showed that aprepitant significantly reduced both the median number of emetic episodes by 1.5 and the median number

1. Matthew Cummings1, Daniel Zlott, PharmD, BCOP2
National Institutes of Health Clinical Center Pharmacy Department, Bethesda, MD
1University of California San Francisco; 2National Institutes of Health
Purpose
1. To determine, using retrospective data in the NIH Clinical Center
database, whether patients who are refractory to other antiemetics
receive clinical benefit from off-label administration of aprepitant for
breakthrough chemotherapy-induced nausea and vomiting (CINV).
2. To determine the extent of nausea before and after aprepitant
administration by using surrogate markers such as number of
emetic episodes and use of other PRN (as needed) breakthrough
medications.
3. To determine if a more robust prospective study of aprepitant
treatment for breakthrough CINV is warranted.
Methods
Retrospective data was collected from the NIH Clinical Center CRIS
database on metastatic melanoma patients undergoing experimental
immunotherapy in trials between August 2007 and May 2015.
Primary Objective
Compare the difference in emetic episodes 48 hours before and 48
hours after aprepitant administration.
Secondary Objective
Compare the difference in PRN (as needed) antiemetic use 48 hours
before and 48 hours after aprepitant administration.
Inclusion Criteria
1. Received a preparative regimen with cyclophosphamide
60mg/kg/day x2 days
2. Aprepitant given >24 hours after the end of last
cyclophosphamide dose
3. Enrolled in an Adoptive Cell Transfer (ACT) protocol at the
National Cancer Institute
Exclusion Criteria
1. Scheduled anti-emetics given within 12 hours prior to aprepitant
dosing
2. Patients for whom data was incomplete
Conclusions
1. Aprepitant is effective at reducing emetic episodes following a
highly emetogenic preparative regimen with cyclophosphamide in
patients with metastatic melanoma.
2. Administering aprepitant reduced patient reliance on other PRN
antiemetics for at least 48 hours after cylcophosphamide.
3. These results strongly support the need for a prospective
randomized controlled trial to determine the efficacy of aprepitant in
this setting.
Disclosures: The authors have no disclosures to report.
Aprepitant as treatment for delayed-onset chemotherapy-induced nausea and
vomiting following a preparative cyclophosphamide regimen
Figure 3 Aprepitant Administration. Chemotherapy schedule and
administration frequency of aprepitant throughout study period.
Statistics
A Wilcoxon Signed-Rank test was used to analyze the primary and secondary
objectives. Non-responders were defined as patients who received scheduled
anti-emetics beginning within 48 hours after aprepitant dosing, or patients who
did not meet a predefined response of 50% reduction in emetic episodes.
Table 1 Response to aprepitant treatment. Total patients administered
aprepitant in the study period, patients excluded, “non-responders” , and
response percentage.
Total
patients
Exclusions Non-
responders
Responders Response %
98 18 20 60 66.6%
2-045
Emetic Episodes PostEmetic Episodes Pre
2.0
1.5
1.0
0.5
0.0
NumberofEpisodes
Number of Emetic Episodes Pre- and Post-Aprepitant Administration
95% CI for the Mean
Grey bars = Median
Blue brackets = 95% CI
PRN Administrations PostPRN Administrations Pre
7
6
5
4
3
2
1
0
NumberofPRNAdministrations
Number of PRN Antiemetics Pre- and Post-Aprepitant Administration
95% CI for the Mean
Grey bars = Median
Blue brackets = 95% CI
Results
Secondary Outcome
The median reduction in PRN
antiemetic use was 2.5
administrations per patient
(95% CI 1.5-3.0; P<0.001).
Primary Outcome
The median reduction in emetic
episodes was 1.5 episodes per
patient (95% CI 1.00-1.5; P
<0.001).
Figure 1 Primary Outcome. Median number of emetic episodes (grey bar) pre- and
post-aprepitant administration with 95% confidence interval (blue bracket).
Figure 2 Secondary Outcome. Median number of PRN antiemetic administrations (grey
bar) pre- and post aprepitant administration with 95% confidence interval (blue bracket).