Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial

Weinstein, Cindy; Jordan, Karin; Green, S. A.; Camacho, Elber S.; Khanani, S.; Beckford-Brathwaite, Elizabeth; Vallejos, Waldimir; Li, Liang; Noga, S. J.; Rapoport, Bernardo

doi:10.1093/annonc/mdv482

Cited by 63 publications

(72 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, a consistent clinically meaningful benefit of approximately 10% to 14% with the addition of an NK‐1 RA for patients receiving carboplatin‐based chemotherapy has begun to emerge in the literature 2, 16, 17. In a recent double‐blind, randomized phase 3 study of patients receiving non–AC‐based MEC, 53% of whom received carboplatin‐based chemotherapy, the addition of fosaprepitant to a 5‐HT 3 RA and dexamethasone regimen provided absolute benefits of 10.4% and 10.2% for a CR in the delayed phase and the overall phase, respectively 18. The addition of aprepitant to standard antiemetic regimens yielded absolute benefits of 14% for the measure of no emesis in the overall phase16, 19 and for the CR rate in the overall phase20 in carboplatin‐treated patients.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

Hesketh

Schnadig

Schwartzberg

et al. 2016

Cancer

View full text Add to dashboard Cite

BACKGROUNDRolapitant, a novel neurokinin‐1 receptor antagonist, provided effective protection against chemotherapy‐induced nausea and vomiting (CINV) in a randomized, double‐blind phase 3 trial of patients receiving moderately emetogenic chemotherapy or an anthracycline and cyclophosphamide regimen. The current analysis explored the efficacy and safety of rolapitant in preventing CINV in a subgroup of patients receiving carboplatin.METHODSPatients were randomized 1:1 to receive oral rolapitant (180 mg) or a placebo 1 to 2 hours before chemotherapy administration; all patients received oral granisetron (2 mg) on days 1 to 3 and oral dexamethasone (20 mg) on day 1. A post hoc analysis examined the subgroup of patients receiving carboplatin in cycle 1. The efficacy endpoints were as follows: complete response (CR), no emesis, no nausea, no significant nausea, complete protection, time to first emesis or use of rescue medication, and no impact on daily life.RESULTSIn the subgroup administered carboplatin‐based chemotherapy (n = 401), a significantly higher proportion of patients in the rolapitant group versus the control group achieved a CR in the overall phase (0‐120 hours; 80.2% vs 64.6%; P < .001) and in the delayed phase (>24‐120 hours; 82.3% vs 65.6%; P < .001) after chemotherapy administration. Superior responses were also observed by the measures of no emesis, no nausea, and complete protection in the overall and delayed phases and by the time to first emesis or use of rescue medication. The incidence of treatment‐emergent adverse events was similar for the rolapitant and control groups.CONCLUSIONSRolapitant provided superior CINV protection to patients receiving carboplatin‐based chemotherapy in comparison with the control. These results support rolapitant use as part of the antiemetic regimen in carboplatin‐treated patients. Cancer 2016;122:2418–2425. © 2016 American Cancer Society.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

Hesketh

Schnadig

Schwartzberg

et al. 2016

Cancer

View full text Add to dashboard Cite

show abstract

“…Data suggest that carboplatin, although less emetogenic than cisplatin, is perhaps on the higher end of emetogenic potential within the MEC classification. [21][22][23][24] Several trials and a subset analysis have shown benefit in terms of complete response (CR) in the overall and delayed phases with the addition of a neurokinin-1 (NK1) receptor antagonist (RA) to the 2-drug regimen of a 5-HT3 antagonist and dexamethasone for the prevention of CINV associated with carboplatin-based regimens, thereby affirming the higher emetogenic potential of carboplatin. [21][22][23][24] All of the commercially available NK1 RAs have an FDA-approved indication for MEC chemotherapy, but previous versions of the NCCN Guidelines have supported the addition of an NK1 RA only for select patients receiving MEC with additional CINV risk factors or in those for whom previous therapy with a steroid and 5-HT3 antagonist alone failed.…”

Section: Emetogenicity Of Chemotherapymentioning

confidence: 99%

“…UC San Diego Moores Cancer Center; 22 UCSF Helen Diller Family Comprehensive Cancer Center; 23 St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 24 Memorial Sloan Kettering Cancer Center; 25 Roswell Park Cancer Institute; 26 University of Michigan Comprehensive Cancer Center; and 27 National Comprehensive Cancer Network.…”

mentioning

confidence: 99%

NCCN Guidelines Insights: Antiemesis, Version 2.2017

Berger¹,

Ettinger²,

Aston³

et al. 2017

J Natl Compr Canc Netw

182

127

View full text Add to dashboard Cite

“…Recently, fosaprepitant was evaluated in a phase III trial that compared a single-day, fosaprepitant-containing antiemetic triplet regimen to a standard 3-day 5-HT 3 RA–dexamethasone regimen in patients treated with MEC [47]. Randomized patients received single-dose (1) fosaprepitant in combination with ondansetron–dexamethasone or (2) ondansetron–dexamethasone on day 1.…”

Section: Introductionmentioning

confidence: 99%

Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists

Bošnjak

Gralla

Schwartzberg

2017

Support Care Cancer

View full text Add to dashboard Cite

Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK1RAs when combined with 5-HT3RA–dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron–dexamethasone) combination in nausea control after cisplatin– or anthracycline–cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). Recently, dexamethasone and dexamethasone–metoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant–dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NK1RAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant–granisetron–dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NK1RAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment.

show abstract

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial

Cited by 63 publications

References 18 publications

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

NCCN Guidelines Insights: Antiemesis, Version 2.2017

Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists

Contact Info

Product

Resources

About