Fosaprepitant dimeglumine (Emend, Merck) is now approved in the United States as a single-use injection to prevent delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC); it is already approved for use in highly emetogenic chemotherapy.
The drug is a substance P/neurokinin-1 (NK1) receptor antagonist indicated for use in combination with other antiemetic medicines, but only as prophylaxis because it has not been studied as a treatment for established nausea and vomiting.
The US Food and Drug Administration (FDA) approval of this new indication of MEC was based in part on findings from a phase 3 study that compared a single intravenous infusion fosaprepitant dimeglumine in combination with ondansetron and dexamethasone with a control regimen.
The results were published in the January issue of the Annals of Oncology.
Although the drug has been approved for the prevention of chemotherapy-induced nausea and vomiting associated with MEC or highly emetogenic chemotherapy, the utility of NK1 receptor antagonists in recipients of nonanthracycline and cyclophosphamide MEC is a matter of debate, according to principal investigator Bernardo L. Rapoport, MD, chief medical oncologist at the Medical Oncology Centre of Rosebank in Johannesburg, and his colleagues.
Their study is the first to directly assess the efficacy and safety of a single intravenous (IV) dose of fosaprepitant in a well-defined noncyclophosphamide MEC population.
In 502 patients in the fosaprepitant group received fosaprepitant 150 mg in combination with the 5-HT₃ receptor antagonist ondansetron 8 mg and the corticosteroid dexamethasone 12 mg, both administered orally, on day 1, followed by oral placebo on days 2 and 3.
The 498 patients in the control group received placebo (IV saline) in combination with ondansetron 8 mg and dexamethasone 20 mg on day 1, followed by ondansetron 8 mg on days 2 and 3.
The primary end point of the study was complete response, defined as no vomiting and no use of rescue medication 25 to 120 hours after initiation of the first dose of MEC (delayed phase).
The rate of complete response was better in the fosaprepitant group than in the control group (78.9% vs 68.5%; P < .001).
The most common adverse reactions in the fosaprepitant and control groups were fatigue (15% vs 13%), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremities (2% vs 1%).
Secondary and exploratory efficacy end points — including vomiting in the overall and delayed phases, nausea in the overall phase, and quality of life — were significantly better in the fosaprepitant group than in the control group, and were consistent with those seen in previous trials of NK1 receptor antagonist.
"This is a very important study and, to me, a practice-changing study," Dr Rapoport said when the results were presented last year at the Multinational Association of Supportive Care in Cancer (MASCC) Annual Meeting.
However, details are missing, Fausto Roila, MD, chair of the Medical Oncology Division at Santa Maria Hospital in Terni, Italy, said at the MASCC meeting.
"Because the category of 'MEC' included drugs with a very wide risk of emesis (between 30% and 90%), it is necessary to know the results achieved with the addition of fosaprepitant in the different MEC drugs," he told Medscape Medical News. "This would permit us to change guidelines accordingly."
This study was supported by Merck & Co. Dr Rapoport and Dr Roila have disclosed no relevant financial relationships. Several coauthors report relationships with industry, as noted in the publication.
Ann Oncol. 2016;27:172-178. Abstract