Merck, a global healthcare leader, announced results from a phase 3 study investigating the safety and efficacy of single-dose Emend (fosaprepitant dimeglumine) for injection, a substance P/neurokinin (NK-1) receptor antagonist, in combination with other anti-vomiting medicines, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adult cancer patients receiving moderately emetogenic (vomit-inducing) chemotherapy (MEC).
In the study, the first to evaluate an intravenous NK-1 receptor antagonist for the prevention of CINV associated with MEC, the single-dose Emend for injection regimen provided greater protection from nausea and vomiting following administration of chemotherapy versus an active control of placebo with other anti-vomiting medicines. These data were presented in an oral session at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual Meeting on Supportive Care in Cancer (Abstract #27-02-O) in Copenhagen held from June 25-27, 2015.
“The results from this important phase 3 trial are very encouraging as they are the first study to evaluate Emend for injection in a combination regimen for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy – and show the potential to use a single day antiemetic regimen,” said Dr. Bernardo L. Rapoport, principal investigator for the study and chief medical oncologist, Medical Oncology Centre of Rosebank, Johannesburg, South Africa.
"Nausea and vomiting remain a significant burden for patients receiving chemotherapy and we look forward to submitting these data for Emend for injection to the US Food and Drug Administration,” said Stuart Green, vice president, clinical research, Merck Research Laboratories. “This study builds on our decade of research for Emend and Merck’s overall commitment to help people with cancer.”
Emend for injection, approved for use in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer (HEC) chemotherapy, including high-dose cisplatin; and for prevention of nausea and vomiting associated with initial and repeat courses of MEC. Emend has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of Emend is not recommended.
In the US, the single-dose regimen of Emend for injection is approved for use associated with HEC. Merck plans to submit these recent data to the Food and Drug Administration in the second half of 2015 to seek approval for a regimen containing single-dose Emend for injection for the prevention of CINV associated with MEC.
In the global randomized, phase 3, double-blind study, more than 1,000 patients receiving MEC were randomly assigned to receive either single-dose Emend for injection (150 mg) in combination with ondansetron capsules (16 mg) and dexamethasone capsules (12 mg) (n=504) on day one (followed by oral placebo for ondansetron on days two and three) or an active control regimen consisting of placebo (saline IV) in combination with ondansetron (16 mg) and dexamethasone (20 mg) (n=497) on day one (followed by 8 mg ondansetron on days two and three). The primary endpoint of the study was complete response (CR) (as measured by no vomiting and no use of rescue medication for nausea or vomiting) in the delayed phase (25 to 120 hours following initiation of chemotherapy). The secondary endpoints were CR after the first dose of chemotherapy in the acute phase (0 to 24 hours) and in the overall phase (0-120 hours), as well as no vomiting in the overall phase.
For the primary study endpoint, Emend for injection regimen provided higher incidence of CR in days 2 through 5 – with CR observed in 78.9 per cent of patients receiving the Emend for injection regimen versus 68.5 per cent in the active control group (p <0.001). For the secondary endpoints, in the acute phase, CR was observed in 93.2 per cent of patients receiving the Emend for injection regimen versus 91 per cent in the active control group (p = 0.184). In the overall phase, the incidence of CR was observed in 77.1 per cent of patients receiving the Emend for injection regimen versus 66.9 per cent in the active control group (p <0.001). Additionally, a significantly greater proportion of patients receiving the Emend for injection regimen experienced no vomiting in the overall phase (82.7 per cent with Emend vs 72.9 per cent in the active control group) and delayed phase (83.9 percent with Emend vs 75.1 per cent in the active control group) (both p <0.001) – with a favorable trend in the acute phase (94.8 per cent with Emend vs 92 per cent in the active control group).
The most common adverse events (across all grades) in the Emend for injection regimen and active control group included fatigue (15.1 per cent and 12.9 per cent), diarrhea (12.7 per cent and 11.3 per cent), and constipation (9.3 per cent and 10.5 per cent). Treatment-related adverse events were observed in 8.5 per cent of patients receiving the Emend for injection regimen and in 9.1 per cent of patients in the active control group. Serious treatment-related adverse events were observed in 0.2 per cent of patients receiving the Emend for injection regimen and in 0.4 per cent of patients in the active control group.
Chemotherapy Induced Nausea and Vomiting (CINV) is a common side effect of chemotherapy caused by injured stomach cells that start the process of nausea and vomiting and can directly activate the area of the brain responsible for producing nausea and vomiting. The two main types of CINV are acute and delayed. Acute happens within the first 24 hours of receiving chemotherapy. Delayed happens from day 2 to day 5 after chemotherapy. The amount and timing of CINV can vary. Some chemotherapies cause acute nausea and vomiting. Others cause acute nausea and vomiting followed by another period of delayed nausea and vomiting.