The emetic response to chemotherapy is now thought to occur through both a peripheral and a central pathway. Several neurotransmitters, including dopamine, serotonin (5-HT), and substance P, are now well established as important mediators of CINV. Not only can CINV have a detrimental effect on patients’ quality of life, but it can also lead to chemotherapy dose reductions or discontinuation, thereby negatively impacting a patient’s response to treatment.Īdvances over the past three decades have not only helped elucidate mechanisms by which chemotherapeutic agents induce nausea and vomiting, but the American Society of Clinical Oncology (ASCO) has recognized the development of effective antiemetic therapies among the top five advances in oncology over the last 50 years. Ĭhemotherapy-induced nausea and vomiting (CINV) is a common distressing side effect associated with many chemotherapeutic drugs and regimens. To view digital features for this article go to. This article is published with digital features, including an infographic, to facilitate understanding of the article. It may be prudent for clinicians to continue to assess these symptoms beyond the traditional 5-day period after cisplatin-based chemotherapy. This exploratory analysis utilized a last observation carried forward (LOCF) approach for missing values for the complete response evaluation.Ĭomplete response rates were numerically higher for fosnetupitant than fosaprepitant during all time intervals and significantly higher for fosnetupitant in the extended overall 0–168 h phase. The primary analysis of this study (previously published) showed non-inferiority of fosnetupitant and fosaprepitant for overall 0–120 h complete response (no emetic event and no rescue medication) rates. fosaprepitant) antiemetic regimens beyond the 120 h time point for prevention of cisplatin-based highly emetogenic CINV. This was the first study to compare two neurokinin 1 (NK 1) receptor antagonist (RA)-containing (fosnetupitant vs. InfographicĬhemotherapy-induced nausea and vomiting (CINV) is described as occurring in two arbitrarily defined phases: the acute phase (from 0 to 24 h following chemotherapy initiation) and the delayed phase (from 24 h to 120 h), with almost all antiemetic studies evaluating treatment efficacy only to 120 h after the administration of chemotherapy. In this exploratory analysis, fosnetupitant appeared to be more effective than fosaprepitant in preventing CINV associated with cisplatin-based HEC during the extended 7-day period following chemotherapy. Complete response rates were numerically higher for fosnetupitant versus fosaprepitant for all time intervals and statistically significant for the extended overall phase. Complete response rates for fosnetupitant versus fosaprepitant during the overall, acute, delayed, extended delayed, beyond delayed, and extended overall phases were 75.5% vs. ResultsĪ total of 785 patients were included (fosnetupitant N = 392, fosaprepitant N = 393). Complete response rates were calculated and compared (stratified by age category and sex with a Mantel–Haenszel test) during the study’s primary overall phase (0–120 h) and during additional time intervals of interest. Patients scheduled to receive cisplatin-based chemotherapy were randomized 1:1 to fosnetupitant 235 mg or fosaprepitant 150 mg in combination with PALO 0.75 mg and DEX. This analysis was performed to validate the findings of the primary analysis (previously published) utilizing a last observation carried forward (LOCF) approach for missing values for the efficacy endpoint of complete response (no emetic event and no rescue medication), while also evaluating the time periods encompassing the 0–168-hour (h) “extended overall phase” interval. We describe the results of an exploratory analysis performed on the first head-to-head study (JapicCTI-194611) comparing two different intravenous (IV) neurokinin 1 (NK 1) receptor antagonists, fosnetupitant and fosaprepitant, in combination with palonosetron (PALO) and dexamethasone (DEX) for the prevention of highly emetogenic chemotherapy (HEC)-induced nausea and vomiting (CINV).
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