Abstract 920
Background
The antiemetic standard of care recommended by guidelines for prevention of CINV in patients receiving cisplatin- and AC-based CT is the combination of an NK1 RA, a 5-HT3 RA, and dexamethasone (DEX). An IV formulation of NEPA (fixed combination of the NK1 RA, fosnetupitant and 5-HT3 RA, palonosetron) was recently approved in the US and is under review in Europe. Approval of IV NEPA was based on showing pharmacokinetic bioequivalence of IV fosnetupitant to oral netupitant and similar safety of IV NEPA to oral NEPA in a phase III study in patients receiving cisplatin-based CT. An IV/oral NEPA safety-controlled phase IIIb study was recently completed in patients receiving AC CT. In both studies, there were no injection-site or hypersensitivity reactions associated with IV NEPA. This secondary analysis presents the efficacy of IV NEPA relative to that of oral NEPA and other NK1 RAs in cisplatin and AC settings.
Methods
Data is compiled from 5 pivotal NEPA studies in a total of 2077 adult chemotherapy-naïve patients with solid tumors undergoing either cisplatin- or AC-based CT. IV NEPA was administered as a single 30-min infusion; oral NEPA was given as a single capsule 60 min prior to CT. Patients also received DEX. Data was also reviewed from 9 phase III cisplatin and AC studies with other NK1 RA (aprepitant [APR], fosaprepitant [FOS], rolapitant [ROL]) regimens. No emesis rates are summarized for the overall phase (0-120h) of the initial cycle of CT. No formal statistical comparisons were performed.
Results
The overall no emesis rates of > 80% for IV NEPA were similar to oral NEPA in both cisplatin and AC settings and were favorable in the context of historical NK1 RA regimens.Table:
1765P
Setting/Study | IV NEPA + DEX | Oral NEPA + DEX | APR + 5-HT3RA + DEX | FOS + 5-HT3RA + DEX | ROL + 5-HT3RA + DEX |
---|---|---|---|---|---|
Cisplatin | |||||
Schwartzberg 2018 | 84.2% | 88.6% | - | - | |
Hesketh 2014 | - | 91.1% | - | - | |
Zhang 2018 | - | 75.0% | - | - | |
Grunberg 2011 | - | - | 74.6% | 72.9% | |
Hesketh 2003 | - | - | 77.7% | - | - |
Poli-Bigelli 2003 | - | - | 66% | - | - |
Schmoll 2006 | - | - | 76.5% | - | - |
Saito 2013 | - | - | - | 67.6% | - |
Rapoport 2015 (HEC-1) | - | - | - | - | 75% |
Rapoport 2015 (HEC-2) | - | - | - | - | 71% |
AC | |||||
Schwartzberg 2019 | 82.5% | 86.1% | - | - | - |
Aapro 2014 | - | 79.8% | - | - | - |
Warr 2005 | - | - | 76% | - | - |
Schwartzberg 2016 | - | - | - | - | 72.4% |
Conclusions
Both IV and oral formulations of NEPA along with DEX represent highly effective guideline-compliant single-dose antiemetics.
Clinical trial identification
NCT03403712.
Editorial acknowledgement
Jennifer Vanden Burgt, Minneapolis, MN, funded by Helsinn Healthcare, Lugano, Switzerland.
Legal entity responsible for the study
Helsinn Healthcare.
Funding
Helsinn Healthcare.
Disclosure
L. Schwartzberg: Advisory / Consultancy, Research grant / Funding (institution): Helsinn Healthcare ; Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: Merck ; Advisory / Consultancy: Heron. M.S. Aapro: Advisory / Consultancy, Research grant / Funding (institution): Helsinn Healthcare; Advisory / Consultancy: Mundipharma; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Merck; Advisory / Consultancy: G1 Therapeutics.
Resources from the same session
592 - Effects of novel targeted anticancer drugs on cytotoxicity, apoptosis, angiogenesis, EMT, drug resistance and autophagic mechanism
Presenter: Seyma Aydinlik
Session: Poster Display session 1
Resources:
Abstract
3235 - Delineating the mechanisms of alpha 1-3 fucosyltransferase FUT11 in ovarian cancer
Presenter: Qi Chen
Session: Poster Display session 1
Resources:
Abstract
3577 - The tyrosine kinase inhibitor Dasatinib blocks tumor growth, invasion and recurrence potential by interrupting the communication between cancer cells and their surrounding microenvironment in triple negative breast cancer
Presenter: Miriam Nuncia-Cantarero
Session: Poster Display session 1
Resources:
Abstract
4808 - NORE1A induces a feedback termination of TNF signaling by antagonizing TNFR1 through ITCH-mediated destruction complex
Presenter: Jieun Ahn
Session: Poster Display session 1
Resources:
Abstract
1294 - Hsp90 inhibitors enhance the antitumoral effect of osimertinib and overcome osimertinib resistance in non-small-cell cell lung cancer cell models
Presenter: Jordi Codony-Servat
Session: Poster Display session 1
Resources:
Abstract
1559 - Expression of IL-17RA promotes cancer stem-like properties of colorectal cancer cells by Stat3 activation
Presenter: Chih-Yung Yang
Session: Poster Display session 1
Resources:
Abstract
1615 - Adaption of Pancreatic Cancer Cells to AKT1 Inhibition Induces the Acquisition of Cancer Stem-Cell Like Phenotype Through Upregulation of Mitochondrial Functions
Presenter: Hugo Arasanz
Session: Poster Display session 1
Resources:
Abstract
4793 - Bub3 is phosphorylated by the Ataxia-Telangiectasia Mutated Kinase in mitosis and required for activation of the mitotic spindle checkpoint in Breast Cancer
Presenter: Mingming Xiao
Session: Poster Display session 1
Resources:
Abstract
1448 - The regulation of INK4 locus by long non-coding RNAs
Presenter: Yojiro Kotake
Session: Poster Display session 1
Resources:
Abstract
1858 - Vascular Endothelial Growth Factor in Colorectal Cancer Pathology, Survival and Treatment
Presenter: Liz Baker
Session: Poster Display session 1
Resources:
Abstract