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

Harry Raftopoulos, William Cooper, Erin O’Boyle, Nashat Gabrail, Ralph Boccia, Richard J. Gralla

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)723-732
Number of pages10
JournalSupportive Care in Cancer
Volume23
Issue number3
DOIs
StatePublished - 2014

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Granisetron
Nausea
Vomiting
Drug Therapy
palonosetron

Keywords

  • APF530
  • Cancer
  • Chemotherapy-induced nausea and vomiting (CINV)
  • Extended-release
  • Granisetron
  • Subcutaneous

ASJC Scopus subject areas

  • Oncology

Cite this

@article{a75c004c44c1417bac91f2b7cd7cf369,
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 = "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.",
keywords = "APF530, Cancer, Chemotherapy-induced nausea and vomiting (CINV), Extended-release, Granisetron, Subcutaneous",
author = "Harry Raftopoulos and William Cooper and Erin O’Boyle and Nashat Gabrail and Ralph Boccia and Gralla, {Richard J.}",
year = "2014",
doi = "10.1007/s00520-014-2400-3",
language = "English (US)",
volume = "23",
pages = "723--732",
journal = "Supportive Care in Cancer",
issn = "0941-4355",
publisher = "Springer Verlag",
number = "3",

}

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.

PY - 2014

Y1 - 2014

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

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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

VL - 23

SP - 723

EP - 732

JO - Supportive Care in Cancer

JF - Supportive Care in Cancer

SN - 0941-4355

IS - 3

ER -