TY - JOUR
T1 - 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
T2 - results of a prospective, randomized, double-blind, noninferiority phase 3 trial
AU - Raftopoulos, Harry
AU - Cooper, William
AU - O’Boyle, Erin
AU - Gabrail, Nashat
AU - Boccia, Ralph
AU - Gralla, Richard J.
N1 - Funding Information:
The authors would like to thank the many investigators and their clinical staff who made this study possible and thank the employees at Heron Therapeutics, Inc. (formerly A.P. Pharma, Inc.) and their service providers who worked very hard to execute and complete one of the largest CINV studies to date. Erin O’Boyle was an employee at A.P. Pharma at the initiation of the manuscript and is currently employed at FibroGen, Inc., 409 Illinois Street, San Francisco, CA 94158. Medical writing support was provided by Yvonne E. Yarker, PhD, CMPP, of SciStrategy Communications, and was funded by Heron Therapeutics, Inc. (formerly A.P. Pharma, Inc.).
Publisher Copyright:
© 2014, The Author(s).
PY - 2015/3
Y1 - 2015/3
N2 - Purpose: 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.
AB - Purpose: 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.
KW - APF530
KW - Cancer
KW - Chemotherapy-induced nausea and vomiting (CINV)
KW - Extended-release
KW - Granisetron
KW - Subcutaneous
UR - http://www.scopus.com/inward/record.url?scp=84922268387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922268387&partnerID=8YFLogxK
U2 - 10.1007/s00520-014-2400-3
DO - 10.1007/s00520-014-2400-3
M3 - Article
C2 - 25179689
AN - SCOPUS:84922268387
SN - 0941-4355
VL - 23
SP - 723
EP - 732
JO - Supportive Care in Cancer
JF - Supportive Care in Cancer
IS - 3
ER -
