Efficacy and safety of palonosetron as salvage treatment in the prevention of chemotherapy-induced nausea and vomiting in patients receiving low emetogenic chemotherapy (LEC)

PURPOSE We evaluated the efficacy and safety of fosnetupitant (FosNTP) versus fosaprepitant (FosAPR) for preventing highly emetogenic chemotherapy-induced nausea and vomiting. This phase III study was the first head-to-head comparison between two different neurokinin-1 receptor antagonists in combination with palonosetron and dexamethasone. PATIENTS AND METHODS Patients scheduled to receive cisplatin-based chemotherapy were randomly assigned 1:1 to FosNTP 235 mg or FosAPR 150 mg in combination with palonosetron 0.75 mg and dexamethasone. The primary end point was overall (0-120 hours) complete response (CR; no emetic event and no rescue medication) rate, stratified by sex and age category, to show the noninferiority of FosNTP to FosAPR (noninferiority margin, –10% for the difference in the overall CR rate). RESULTS Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP [N = 392] v FosAPR [N = 393]) and were evaluated for efficacy and safety. The overall CR rate was 75.2% versus 71.0%, respectively (Mantel-Haenszel common risk difference, 4.1%; 95% CI, –2.1% to 10.3%), demonstrating noninferiority of FosNTP to FosAPR. The CR rates in the acute (0-24 hours), delayed (24-120 hours), and beyond delayed (120-168 hours) phases, and at 0-168 hours were 93.9% versus 92.6%, 76.8% versus 72.8%, 86.5% versus 81.4%, and 73.2% versus 66.9%, respectively. The incidence rates of treatment-related adverse events with FosNTP versus FosAPR were 22.2% versus 25.4%, whereas adverse events or treatment-related adverse events relevant to injection site reactions were 11.0% versus 20.6% ( P < .001) and 0.3% versus 3.6% ( P < .001), respectively. CONCLUSION FosNTP demonstrated noninferiority to FosAPR, with a favorable safety profile and lower risk for injection site reactions. Thus, FosNTP is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.

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Efficacy and safety of fosaprepitant in the prevention of nausea and vomiting following highly emetogenic chemotherapy in Chinese people: A randomized, double-blind, phase III study

European Journal of Cancer Care ◽

10.1111/ecc.12668 ◽

2017 ◽

Vol 26 (6) ◽

pp. e12668

Author(s):

L.Q. Yang ◽

X.C. Sun ◽

S.K. Qin ◽

Y. Cheng ◽

J.H. Shi ◽

...

Keyword(s):

Emetogenic Chemotherapy ◽

Nausea And Vomiting ◽

Phase Iii ◽

Efficacy And Safety ◽

Chinese People ◽

Highly Emetogenic Chemotherapy ◽

Double Blind ◽

Phase Iii Study

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Efficacy and Safety of Palonosetron in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients with Non-Hodgkin's Lymphomas Undergoing Repeated Cycles of Moderately Emetogenic Chemotherapy

Blood ◽

10.1182/blood.v118.21.5196.5196 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5196-5196

Author(s):

Brian Choi ◽

Gabriela Borsaru ◽

Daniel Voisin ◽

Gianluca Ballinari ◽

Nicola Di Renzo

Keyword(s):

Adverse Events ◽

Complete Response ◽

Emetogenic Chemotherapy ◽

Nausea And Vomiting ◽

Negative Consequences ◽

Efficacy And Safety ◽

Moderately Emetogenic Chemotherapy ◽

Antiemetic Prophylaxis ◽

Secondary Endpoints ◽

Hodgkin's Lymphomas

Abstract Abstract 5196 Background: Patients undergoing chemotherapy (CT) commonly receive repeated cycles of treatment. While chemotherapy-induced nausea and vomiting (CINV) can be a disruptive, unwanted side effect with negative consequences on patient quality of life, possible discontinuation of therapy, and associated increased health care resources, prevention of CINV in cycle 1 diminishes its potential in subsequent cycles. Therefore, optimizing antiemetic prophylaxis at initiation of CT is critical. Palonosetron (PALO), a potent 5-HT3 receptor antagonist (RA) with a distinctly different pharmacokinetic and receptor binding profile, has demonstrated improved CINV protection compared to older 5-HT3 RAs in multiple phase 3 and 4 single-CT-cycle clinical trials; however, few studies have evaluated PALO over multiple cycles of CT. Methods: This was a prospective, multicenter, single-arm study designed to assess the efficacy and safety of single IV doses of PALO 0.25 mg in preventing CINV in chemotherapy-naïve patients with Non-Hodgkin's Lymphomas (NHL) scheduled to receive at least 2 repeated, consecutive cycles of moderately emetogenic chemotherapy (CHOP, R-CHOP or ProMACE-CytaBOM). Corticosteroids were part of the CT regimen but not administered as an antiemetic. The primary efficacy endpoint was complete response (CR: defined as no emesis and no use of rescue medication) during the overall phase (0–120 h) following CT during each cycle. Secondary endpoints included CR during the acute (0–24 h) and delayed (24–120 h) time periods, as well as evaluation of proportion of emesis-free patients and nausea severity (according to a 100 mm VAS) during all 3 time intervals. The safety profile and adverse events were also assessed. Results: A total of 88 patients with either B-cell (91%) or T-cell (9%) NHL received PALO for a total of 317 CT cycles (mean 3.6; median 4). The majority of patients were white (99%) males (60%) with a mean age of 59.7 yrs who received either CHOP (47%) or R-CHOP (52%). CR rates during the acute, delayed and overall phases were sustained across the 4 CT cycles (Table). High proportions of patients remained emesis-free and experienced less than significant nausea (0 to <25 mm VAS) during the 5 days post-CT throughout repeated CT cycles (Table). PALO was well tolerated over repeated cycles, with few adverse events considered possibly/probably/definitely related (TRAEs: treatment related adverse events) (8% of patients; none serious). The incidence of the typically frequent TRAEs of headache and constipation was low (1% and 2%) and there were no unexpected or relevant differences in TRAEs between cycles or in later cycles (6%, 3%, 0%, 4% cycles 1–4, respectively). Conclusion: A single, fixed IV dose of palonosetron was shown to be safe and effective in preventing CINV over repeated chemotherapy cycles in patients with NHL. Disclosures: Voisin: Helsinn Healthcare: Employment. Ballinari:Helsinn Healthcare: Employment.

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