PMID- 27000465 OWN - NLM STAT- MEDLINE DCOM- 20161223 LR - 20201209 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 21 IP - 4 DP - 2016 Apr TI - Safety of an Oral Fixed Combination of Netupitant and Palonosetron (NEPA): Pooled Data From the Phase II/III Clinical Program. PG - 494-502 LID - 10.1634/theoncologist.2015-0301 [doi] AB - BACKGROUND: Standard prophylaxis for chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials. MATERIALS AND METHODS: This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures. RESULTS: Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatment-emergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in >/=2% of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6%), tachycardia (1.1%), and dyspnea (0.9%) the most common. Serious cardiac TEAEs were rare. CONCLUSION: NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity. IMPLICATIONS FOR PRACTICE: Supportive care for cancer should ideally be efficacious, convenient, and well-tolerated. There have been concerns about cardiac safety with current antiemetic prophylactic agents, namely dolasetron and ondansetron. This pooled safety analysis demonstrates that the new oral fixed combination therapy NEPA can be safely added to an antiemetic regimen without increased toxicity. CI - (c)AlphaMed Press. FAU - Aapro, Matti AU - Aapro M AD - Clinique de Genolier, Genolier, Switzerland maapro@genolier.net. FAU - Hesketh, Paul J AU - Hesketh PJ AD - Lahey Hospital and Medical Center, Burlington, Massachusetts, USA. FAU - Jordan, Karin AU - Jordan K AD - University of Halle, Halle, Germany. FAU - Gralla, Richard J AU - Gralla RJ AD - Albert Einstein College of Medicine, Bronx, New York, USA. FAU - Rossi, Giorgia AU - Rossi G AD - Helsinn Healthcare, Lugano, Switzerland. FAU - Rizzi, Giada AU - Rizzi G AD - Helsinn Healthcare, Lugano, Switzerland. FAU - Palmas, Marco AU - Palmas M AD - Helsinn Healthcare, Lugano, Switzerland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160321 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antiemetics) RN - 0 (Biomarkers, Pharmacological) RN - 0 (Drug Combinations) RN - 0 (Isoquinolines) RN - 0 (Neurokinin-1 Receptor Antagonists) RN - 0 (Pyridines) RN - 0 (Quinuclidines) RN - 0 (Serotonin 5-HT3 Receptor Antagonists) RN - 0 (netupitant, palosentron drug combination) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Adult MH - Aged MH - Antiemetics/*therapeutic use MH - Biomarkers, Pharmacological MH - Dexamethasone/administration & dosage/adverse effects MH - Drug Combinations MH - Drug Therapy MH - Drug-Related Side Effects and Adverse Reactions/pathology/*prevention & control MH - Female MH - Humans MH - Isoquinolines/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Nausea/chemically induced/pathology/prevention & control MH - Neoplasms/complications/*drug therapy/pathology MH - Neurokinin-1 Receptor Antagonists/therapeutic use MH - Pyridines/adverse effects/*therapeutic use MH - Quinuclidines/adverse effects/*therapeutic use MH - Randomized Controlled Trials as Topic MH - Serotonin 5-HT3 Receptor Antagonists/therapeutic use MH - Vomiting/chemically induced/pathology/prevention & control PMC - PMC4828115 OTO - NOTNLM OT - Antiemetics OT - Chemotherapy OT - Nausea OT - Neurokinin-1 receptor antagonists OT - Safety OT - Serotonin 5-hydroxytryptamine-3 receptor antagonists OT - Vomiting COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2016/03/24 06:00 MHDA- 2016/12/24 06:00 PMCR- 2017/04/01 CRDT- 2016/03/23 06:00 PHST- 2015/07/30 00:00 [received] PHST- 2015/11/02 00:00 [accepted] PHST- 2016/03/23 06:00 [entrez] PHST- 2016/03/24 06:00 [pubmed] PHST- 2016/12/24 06:00 [medline] PHST- 2017/04/01 00:00 [pmc-release] AID - theoncologist.2015-0301 [pii] AID - T15301 [pii] AID - 10.1634/theoncologist.2015-0301 [doi] PST - ppublish SO - Oncologist. 2016 Apr;21(4):494-502. doi: 10.1634/theoncologist.2015-0301. Epub 2016 Mar 21.