title: Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: results of a prospective, randomized, double-blind, noninferiority phase 3 trial.
abstract: OBJECTIVE
  Subcutaneous APF530 provides controlled sustained release of granisetron to prevent acute (0-24 h) and delayed (24-120 h) chemotherapy-induced nausea and vomiting (CINV). This randomized, double-blind phase 3 trial compared APF530 and palonosetron in preventing acute and delayed CINV after moderately (MEC) or highly emetogenic chemotherapy (HEC).
  
  
  METHODS
  Patients receiving single-day MEC or HEC received single-dose APF530 250 or 500 mg subcutaneously (SC) (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg. Primary objectives were to establish APF530 noninferiority to palonosetron for preventing acute CINV following MEC or HEC and delayed CINV following MEC and to determine APF530 superiority to palonosetron for preventing delayed CINV following HEC. The primary efficacy end point was complete response (CR [using CI difference for APF530-palonosetron]). A lower confidence bound greater than -15 % indicated noninferiority.
  
  
  RESULTS
  In the modified intent-to-treat population (MEC = 634; HEC = 707), both APF530 doses were noninferior to palonosetron in preventing acute CINV after MEC (CRs 74.8 % [-9.8, 9.3] and 76.9 % [-7.5, 11.4], respectively, vs. 75.0 % palonosetron) and after HEC (CRs 77.7 % [-11.5, 5.5] and 81.3 % [-7.7, 8.7], respectively, vs. 80.7 % palonosetron). APF530 500 mg was noninferior to palonosetron in preventing delayed CINV after MEC (CR 58.5 % [-9.5, 12.1] vs. 57.2 % palonosetron) but not superior in preventing delayed CINV after HEC. Adverse events were generally mild and unrelated to treatment, the most common (excluding injection-site reactions) being constipation.
  
  
  CONCLUSIONS
  A single subcutaneous APF530 injection offers a convenient alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC.
authors.affiliation: Hofstra North Shore-LIJ School of Medicine, 450 Lakeville Road, Lake Success, NY, 11042, USA, hraftopo@nshs.edu.
authors.forename: Harry
authors.initials: H
authors.lastname: Raftopoulos
authors.forename: William
authors.initials: W
authors.lastname: Cooper
authors.forename: Erin
authors.initials: E
authors.lastname: O'Boyle
authors.forename: Nashat
authors.initials: N
authors.lastname: Gabrail
authors.forename: Ralph
authors.initials: R
authors.lastname: Boccia
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gralla
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D017829:Granisetron / Q000627:therapeutic use*; D006801:Humans; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy*; D000077924:Palonosetron; D011446:Prospective Studies; D011812:Quinuclidines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D003692:Delayed-Action Preparations; D017829:Granisetron; D007546:Isoquinolines; D000077924:Palonosetron; D011812:Quinuclidines