Palonosetron (PALO) plus 1-day versus 3-day dexamethasone (DEX) with or without aprepitant against delayed nausea (DN): Pooled analysis for 554 women receiving highly emetogenic chemotherapy (HEC).

Abstract

9133 Background: Nausea is more difficult to control than vomiting, because the incidence of the symptom continues to rise over the days after chemotherapy. This post-hoc analysis addressed two questions: 1) Does PALO plus single-dose DEX result in suboptimal control of DN when compared to the same regimen with additional DEX doses? 2) Is the combination of PALO, DEX, and aprepitant a more effective coverage against DN? Methods: The analysis was based upon outcomes in chemo-naïve women (median age =52) with solid tumors (89% breast) enrolled in two Phase III and two Phase II trials of HEC (AC combination or cisplatin). Patients received the following regimens: 1) PALO 0.25 mg plus DEX 8 mg IV on day 1 of chemotherapy (1-day regimen, n=243); 2) the same regimen on the day 1 followed by DEX 8 mg orally on days 2 and 3 (3-day regimen, n=207); or PALO plus DEX plus aprepitant 125 mg on day 1 followed by aprepitant 80 mg on days 2 and 3 (triple regimen, n=104). The pre-specified primary endpoint was the proportion of patients with no DN (days 2-5 after the first cycle of chemotherapy). The two primary comparisons were 1-day vs. 3-day regimen, and triple vs. 3-day regimen, with statistical significance set to the 0.025 level. Results: The 1-day to 3-day regimen comparison was not statistically significant (44% vs. 47.8%; risk difference (RD) = -3.8%, 95% CI (-5.4 to 12.9%), P=0.421 (two-sided chi-square test). The triple to 3-day regimen comparison was also not significant (57.7% vs. 47.8%), RD= +9.9%, 95% CI (-1.9 to 21.3%), P=0.101. More patients receiving triple regimen experienced no acute-onset nausea compared with those administered only DEX (97.1% vs. 51.2%, P<0.0001). Conclusions: This analysis provides evidence that PALO plus 1-day or 3-day DEX yield similar prevention of DN. The addition of aprepitant does not improve the control of DN. Complete results utilizing a multivariable model accounting for risk factors and trial heterogeneity will also be presented.