Single-Dose Oral Combination Antiemetic Shows Good Efficacy Over Multiple Cycles
NEPA, a combination of netupitant and palonosetron, provides a convenient and effective way of treating chemotherapy-induced nausea and vomiting
- Date: 18 Mar 2014
- Author: Lucy Piper, Senior medwireNews Reporter
- Topic: Supportive Care
medwireNews: Phase III study results show that NEPA is a convenient and effective treatment for preventing chemotherapy-induced nausea and vomiting over repeated cycles of moderately and highly emetogenic chemotherapy.
NEPA is a single oral fixed-dose combination of the neurokinin (NK)1 Receptor antagonist (RA) netupitant (NETU), which has a long half-life of 90 hours, and the serotonin (5-HT3) RA palonosetron (PALO).
In their study of 308 patients randomly assigned to receive a single dose of NEPA (NETU 300 mg and PALO 0.5 mg) with oral dexamethasone on day 1, the proportion of patients with no significant nausea was high, ranging from 84% to 92% of patients across six cycles of treatment. Patients achieving a complete response, defined as no emesis and no need for rescue medication, exceeded 80% in cycles one and two and 90% across the remaining four cycles.
The rates were comparable to those achieved by patients randomly assigned to an oral 3-day aprepitant regimen plus PALO (APR+PALO) plus dexamethasone, the researchers note. The proportion with no significant nausea ranged from 81% to 87% and complete response rates were 76% to 88% across the six cycles.
The proportion of NEPA-treated patients achieving a complete response was high irrespective of whether patients received highly or moderately emetogenic chemotherapy, at 79–91% and 80–93% across cycles, respectively. By contrast, the rate was modestly lower for highly emetogenic chemotherapy than moderately emetogenic chemotherapy for patients receiving APR+PALO, at 58–86% compared with 82–89%.
The researchers, led by Richard Gralla, from Hofstra North Shore-LIJ School of Medicine, New York, USA, note that over 75% of patients completed at least four cycles of treatment, which “provides confidence in the preservation of antiemetic effect over multiple cycles”.
NEPA was also well tolerated by patients. Adverse events were mainly mild to moderate in severity and although slightly more common in patients receiving NEPA, they remained low, at 10.1% compared with 5.8% for patients receiving APR+PALO. The most frequent NEPA-related events were constipation (3.6%) and headache (1.0%).
Encouragingly, there was no evidence of adverse events increasing or worsening over multiple cycles and there were no cardiac safety concerns with NEPA based on adverse events and electrocardiograms.
“NEPA offers an opportunity to provide effective antiemetic care which is consistent with guideline-recommendations in a maximally convenient combination”, the researchers write in the Annals of Oncology.
They add: “Further studies should be performed to determine if the highly convenient concept of NEPA will result in greater adherence, fostering improved emetic control.”
Gralla R, Bosnjak S, Hontsa A, et al. A phase 3 study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. Ann Oncol 2014; Advance online publication March 14. doi: 10.1093/annonc/mdu096
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