DISCUSSION
emesis, nausea, CINV, anxiety
ONCOLOGY
While most studies demonstrating a clear benefit of an NKIn the primary publication of this study Zelek et al. highlight the trend toward better responses with NEPA versus the aprepitant regimen for the primary endpoint of complete response during the traditional 0–120 h overall phase in both the overall study population and in the MEC group.This differentiation was also seen in previous analyses in the cisplatin setting in all patients and also in those at the greatest emetic risk receiving the highest doses of cisplatin. Navari et al described the pooled results of three studies which included oral NEPA versus an aprepitant regimen.In light of the evidence of this long‐lasting prevention, the current study was uniquely designed to evaluate the comparative efficacy for an extra day beyond that typically assessed (i.e., to 144 h post‐chemotherapy). In this analysis of patients receiving MEC in this study, NEPA showed significantly higher complete response (77.1% vs. 57.8%) and no emesis rates (85.3% vs. 72.5%) than the aprepitant regimen during the extended (0–144 h) overall phase. The high and better response rates for NEPA during the acute phase may have contributed to the significantly better control during the extended overall phase. During the extended delayed phase, the complete response rate was also numerically higher for NEPA (89.9% vs. 83.3%), while no emesis rates were similar for the treatment groups (90.8% vs. 89.2%). Although no significant nausea rates were higher for NEPA than aprepitant during the extended overall phase (70.9% vs. 66.7%) the difference was not statistically significant.There was an incremental benefit of 6.3% in complete response rates in favor of NEPA during the extended overall phase (a 19.3% absolute difference) relative to the traditional overall 0–120 h phase (a 13.0% absolute difference), again suggesting NEPA may exhibit long‐lasting effects. The efficacy benefit seen with NEPA for the study's primary endpoint of complete response and for preventing emesis during the extended overall phase may be due to the differences in plasma elimination half‐lives of netupitant (80–96 h) versus that for aprepitant (9–13 h).Another study also evaluated antiemetic efficacy beyond the traditional 120 h timepoint, in this case up to 168 h.The pre‐defined CINV risk factors of female gender, young age, and anxiety selected in this subset of MEC patients are well‐established for elevating the risk of CINV.While comparative cost‐effectiveness was not evaluated in this study, it is noteworthy that studies have been performed showing NEPA to be more cost‐effective than an aprepitant‐based antiemetic regimen, albeit not in a French population.Limitations of this study/analysis include that it was an open‐label design which, although common in pragmatic trials, is susceptible to bias. Another potential limitation is the imbalance seen for baseline characteristics of gender and carboplatin use. In this MEC group, there was a greater proportion of females receiving the aprepitant regimen than NEPA, but also a greater proportion of NEPA patients received carboplatin, a more emetogenic chemotherapy than oxaliplatin and irinotecan. It is possible that these two differences in factors contributing to emetic risk balanced the groups. And finally, as with all post‐hoc analyses, the importance of these findings must be properly considered in the context of their exploratory characteristic.It is noteworthy that the absolute difference in complete response rates during the extended overall phase was 19% in the total MEC group and 18% in the subset with CINV risk factors. Per the Multinational Association of Supportive Care in Cancer/European Society of Medical Oncology (MASCC/ESMO) guidelines, such large differences (>10%) are clinically meaningful.NEPA is a novel fixed combination antiemetic that simplifies dosing and eliminates the complexity of administering multiple agents and over multiple days (such as is the case with the oral aprepitant regimen), thereby minimizing the potential for non‐compliance with treatment. In this first NK