Fosaprepitant for the Prevention of Nausea and Vomiting in Patients Receiving BEAM or High-Dose Melphalan Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation

Chemotherapy-induced nausea and vomiting (CINV) occurs frequently during hematopoietic stem cell transplantation (HSCT) despite prophylactic therapy with serotonin antagonists and corticosteroids. Aprepitant, an oral neurokinin-1 (NK1) inhibitor, has been considered as add-on prophylactic therapy; however, to date no published studies have investigated the injectable NK1 inhibitor fosaprepitant (FOS) in HSCT. The purpose of this study is to assess the ability of FOS to reduce emesis after BEAM and high-dose melphalan autologous HSCT.

The use of a 150 mg fosaprepitant IV x 1 prior to melphalan became standard practice at our institution in the summer of 2012 for BEAM and high-dose melphalan regimens. We performed an IRB approved cohort study comparing patients who prospectively receive FOS to a historical cohort who did not receive FOS. The primary endpoint was overall percentage of patients with no emesis during the assessment period (first day of melphalan through five days after melphalan administration). Secondary endpoints include number of emetic episodes per patient, number of breakthrough antiemetic doses per patient, and complete response rate (no emesis or breakthrough antiemetic use). Patients in the FOS cohort also recorded nausea on a 100 mm visual analog scale (VAS) daily allowing for additional exploratory endpoints of complete protection rate (complete response plus no significant nausea), no significant nausea (< 25 mm on 100 mm VAS), and no nausea (< 5 mm on 100 mm VAS) to be assessed for that single cohort. A sample size of 70 patients per cohort was deemed necessary based on an estimated 40% no emesis in control group for 80% power at alpha=0.05 to detect a 25% absolute increase in patients with no emesis.

Seventy consecutive patients who received BEAM or high-dose melphalan without FOS were included in the historical cohort and 43 patients have received FOS in the prospective cohort. Interim results suggest the addition of FOS improved the percentage of patients with no emesis and the number of emetic episodes per patient. Exploratory endpoints in the FOS cohort which included patient reported nausea assessments on a VAS are encouraging as a third of patients reported no significant nausea during the overall assessment period. Based on these promising interim results, enrollment in the FOS cohort is ongoing.

Table 1: Results Fosaprepitant vs. Control, Overall Assessment Period

	Control (n=70)	FOS (n=43)
No emesis (%)	65.7	81.4
Day(s) of melphalan (%)	98	99
Days 1-5 post-melphalan (%)	66	84
Complete response (%) (no emesis or breakthrough antiemetic use)	1.4	4.7
Emetic episode per patient (mean)	0.76	0.28
Breakthrough antiemetic doses per patient (mean)	9.6	9.98
Complete protection (%) (no emesis, breakthrough antiemetics, or significant nausea)	-	9.7*
No nausea (%) (<5 mm on 100 mm VAS)	-	16.1*
No significant nausea (%) (<25 mm on 100 mm VAS)	-	35.5*

*For 31 evaluable subjects