title: Efficacy benefit of an NK1 receptor antagonist (NK1RA) in patients receiving carboplatin: supportive evidence with NEPA (a fixed combination of the NK1 RA, netupitant, and palonosetron) and aprepitant regimens.
abstract: Antiemetic guideline recommendations are inconsistent as to whether a neurokinin-1 receptor antagonist (NK1 RA) should be administered with a 5-hydroxytryptamine-3 (5HT3) RA + dexamethasone (DEX) in patients receiving carboplatin. Patients receiving cisplatin routinely receive an NK1 RA-containing regimen with a resulting 14-22 % benefit in no emesis rates over a 5-HT3 RA/DEX control. Recent studies suggest a similar benefit in patients receiving carboplatin. NEPA is the first fixed antiemetic combination agent and comprises the highly selective NK1 RA, netupitant, and pharmacologically distinct 5-HT3 RA, palonosetron (PALO). This paper presents the efficacy of NEPA in the subset of patients receiving carboplatin in a phase 3 trial (NCT01376297), in the context of aprepitant (APR) data in the carboplatin setting.
  
  
  
  One hundred ninety-six patients (47 % of all study patients: n = 145 NEPA + DEX; n = 51 APR + PALO + DEX) received carboplatin in a multinational, double-blind, randomized phase 3 study. Complete response (CR: no emesis/rescue) and no significant nausea (NSN: score ≤25 on 100 mm visual analog scale) rates were calculated.
  
  
  
  Cycle 1-4 overall (0-120 h) CR rates were similar for NEPA (80, 91, 92, and 93 %) and APR (82, 88, 88, and 90 %). Overall NSN rates were also similar (NEPA 84-96 %; APR 82-90 %).
  
  
  
  Response rates for NEPA and APR regimens were similar and consistent with prior studies evaluating the contribution of adding NK1 RAs in patients receiving carboplatin. Considering such evidence, guideline groups/practitioners should consider giving a NK1 RA antiemetic triplet in patients receiving carboplatin.
authors.affiliation: Department for Hematology/Oncology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle, Germany. karin.jordan@uk-halle.de.
authors.forename: Karin
authors.initials: K
authors.lastname: Jordan
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Gralla
authors.affiliation: Helsinn Healthcare, SA, Lugano, Switzerland.
authors.forename: Giada
authors.initials: G
authors.lastname: Rizzi
authors.affiliation: Eisai Inc., Woodcliff Lake, NJ, USA.
authors.forename: Kimia
authors.initials: K
authors.lastname: Kashef
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000077608:Aprepitant; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D000077924:Palonosetron; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D011812:Quinuclidines / Q000008:administration & dosage / Q000627:therapeutic use*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D010879:Piperazines; D044482:Benzeneacetamides
chemical_list: D000077608:Aprepitant; D016190:Carboplatin; D007546:Isoquinolines; D009025:Morpholines; D000077924:Palonosetron; D011725:Pyridines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; C508854:netupitant; D010879:Piperazines; D044482:Benzeneacetamides
keywords: Aprepitant; CINV; Carboplatin; NEPA; Netupitant; Palonosetron