This article is more than 5 years old. Information may no longer be current.
Aprepitant regimen reduced CINV in post-transplant myeloma
The addition of the NK-1 antagonist aprepitant to granisetron and dexamethasone reduced nausea and vomiting among patients with myeloma who underwent high-dose chemotherapy and autologous stem cell transplantation, according to results of a randomized, phase 3 trial.
The analysis included 362 patients with myeloma who melphalan conditioning followed by autologous stem cell transplantation at Heidelberg University Hospital in Germany. All patients were aged 18 years or older.
The study consisted of a 4-day treatment phase, followed by a 3-day follow-up phase.
Researchers randomly assigned half of the patients to receive granisetron (2 mg orally on days 1 to 4), dexamethasone (4 mg orally on day 1, followed by 2 mg orally on days 2 and 3) and aprepitant [(Emend, Merck), 125 mg orally on day 1, and 80 mg on days 2 to 4]. The other half of patients received placebo, granisetron (2 mg orally on days 1 to 4) and dexamethasone (8 mg on day 1, followed by 4 mg on days 2 and 3).
Patients underwent treatment with IV melphalan 100 mg/m2 on days 1 and 2, and they underwent autologous stem cell transplantation on day 4. Rescue treatment for chemotherapy-induced nausea and vomiting (CINV) was at the discretion of the treating clinician.
Overall complete response, defined as freedom from emesis and rescue therapy within 120 hours of melphalan treatment, served as the primary endpoint. Prespecified secondary endpoints included complete response, defined as absence of emesis and rescue therapy in acute (0-24 hours) or delayed (25 to 120 hours) phases; rates of emesis, nausea and significant nausea; number of adverse events and impact on quality of life as measured by Functional Living Index-Emesis (FLIE) score.
Results showed a significantly higher complete response rate among patients assigned aprepitant (58% vs. 41%; OR=1.92; 95% CI, 1.23-3). Researchers also reported higher rates of secondary endpoints — including absence of major nausea (94% vs. 88%; OR=2.37; 95% CI, 1.09-5.15) and emesis (75% vs. 65%; OR=1.99; 95% CI, 1.25 to 3.18) within 120 hours — in the aprepitant arm. Also, patients assigned aprepitant reported improved quality of life (mean FLIE scores, 114 ±18 vs. 106 ± 26; P<.001).
“The prophylactic combination regimen of granisetron, dexamethasone and aprepitant proved to be safe and improve quality of life and significantly reduce CINV,” the researchers wrote. “To our knowledge, it is the largest randomized trial with a homogenous patient population, adding prospective data to the current literature. For patients undergoing high-dose melphalan conditioning, addition of aprepitant to a standard antiemetic regimen should be strongly considered.”
Disclosure: The researchers report consultant or advisory roles with, as well as research funding, honoraria and other remuneration from, Celgene, Chugai, Janssen, Merck Sharp & Dohme, Millennium, Novartis and Onyx.
Collapse