The FDA has expanded the approval of Emend's indication for chemotherapy-induced nausea and vomiting.
The FDA has approved Emend (aprepitant capsules) in combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting in patients aged 12 to 17 and for those under the age of 12 who weigh at least 66 lbs (30 kg) who are receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC).
The extension to the Emend indication was based on findings from a phase 3 clinical trial that examined Emend plus Zofran (ondansetron) compared with placebo and Zofran. The study enrolled 302 patients between the age of six months and 17 years. In those between the age of 12 and 17 or under 12 and at least 66 lbs (132 patients), an acute or delayed complete response (CR), defined as no vomiting or retching, was achieved for 34.9 percent of patients treated with the combination versus 13 percent with Zofran monotherapy.
A CR in the delay phase, defined as 25 to 120 hours following the initiation of chemotherapy, was experienced by 49.2 percent of patients treated with the Emend/Zofran combination compared with 18.8 percent with Zofran alone. In the first 24 hours following treatment (acute phase), 55.6 percent of patients treated with the combination had a CR versus 37.7 percent with Zofran alone.
“The FDA approval of this expanded indication for Emend is the result of our commitment to fully realizing the potential of our therapies to help as many patients as possible,” Stuart Green, vice president, clinical research, Merck Research Laboratories, said in a statement. “Historically, significant improvements in pediatric medicine have been slow due to many challenges such as clinical trial size. However, at Merck, these obstacles have invigorated our efforts to bring forward a new option for these patients.”
In the phase 3 clinical trial, treatment with the NK-1 receptor antagonist Emend was administered at 125 mg on the first day of treatment followed by 80 mg on day 2 and 3. The 5-HT3 receptor antagonist Zofran was administered prior to chemotherapy on day 1 in both arms. Intravenous dexamethasone was permitted, with a 50 percent dose reduction required in the Emend arm. Across the full study, 30 percent of patients received dexamethasone in the first cycle.
Following the first cycle, patients were allowed to receive open-label Emend in cycles 2 to 6. The primary endpoint of the study was CR in the delayed phase. Secondary outcome measures included CR in the acute and overall phase along with safety and tolerability.
Across the full study, 152 patients were treated in the Emend group and 150 were enrolled in the control arm. According to findings published in the Lancet Oncology for the full population of the study, the CR rate in the delayed phase was 50.7 percent with Emend plus Zofran and 26 percent with Zofran alone. In the acute phase, the CR rates were 66.4 and 52 percent with and without Emend, respectively. The overall CR rate across phases was 40.1 percent with Emend and 20 percent with Zofran alone.
All-grade adverse events (AEs) were seen in 79 percent of patients treated with Emend versus 77 percent with Zofran alone. The most frequently observed grade 3/4 AEs with Emend plus Zofran versus Zofran alone, respectively, were febrile neutropenia (15 vs 14 percent), anemia (9 vs 17 percent), and decreased neutrophil count (7 vs 11 percent). Febrile neutropenia was the most common serious AE, and occurred in 15 percent of patients in each arm.
For patients under the age of 12 who weighed less than 66 lbs, an appropriate commercially available dose of Emend is not yet available. In the phase 3 study, an investigational powder for suspension formulation was examined for those below 66 lbs; however, under the Pediatric Research Equity Act (PREA), an application for this formulation is still pending for pediatric patients.
Kang HJ, Loftus S, Taylor A, et al. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16(4):385—394.