Fosaprepitant dosing frequency makes no difference in CCRT-induced nausea, vomiting prevention

For patients undergoing concurrent chemoradiotherapy (CCRT), treatment with either weekly or every-3-weeks fosaprepitant helps reduce nausea and vomiting caused by CCRT, with no difference in the effect, as reported in a study.

In a cohort of patients with nasopharyngeal carcinoma who were scheduled to receive intensity-modulated radiation therapy (IMRT) and concomitant cisplatin every 3 weeks at 100 mg/m², the cumulative risk of complete response, defined by the absence of emesis or rescue therapy during CCRT, was similar in the group that received weekly fosaprepitant and in the group that received fosaprepitant every 3 weeks (subhazard ratio, 0.66, 95 percent confidence interval [CI], 0.43–1.02; p=0.06). [JAMA Netw Open 2023;6:e2326127]

“Although there was no statistically significant difference in the complete response primary endpoint, we found that weekly fosaprepitant was more effective in providing sustained protection against emesis and significant nausea than fosaprepitant every 3 weeks,” the investigators pointed out.

The proportion of patients with sustained no emesis was 38 percent in the weekly group vs 14 percent in the every-3-weeks group (p=0.003), while the respective proportion of patients with no significant nausea was 92 percent vs 72 percent (p=0.002).

Exploratory outcomes

There were interactions between treatment effects and mean brainstem dose of at least 36 Gy, according to the investigators, suggesting that intensified weekly fosaprepitant may have more remarkable antiemetic action in patients with higher mean brainstem dose.

In the mean brainstem dose subgroups, weekly fosaprepitant had a more pronounced benefit in the ≥36 Gy subgroup than in the <36 Gy subgroup for both outcomes of sustained complete response (hazard ratio [HR], 0.32, 95 percent confidence interval [CI], 0.15–0.69 and HR, 0.95, 95 percent CI, 0.55–1.63) and sustained no emesis (HR, 0.21, 95 percent CI, 0.08–0.53 and HR, 0.73, 95 percent CI, 0.41–1.28).

“It is interesting to note that areas connected to the development of emesis also exist in the brainstem,” the investigators said.

“Multiple studies have reported a radiation dose–response association of brainstem dose with nausea and vomiting symptoms, which may contribute to a higher incidence of nausea and vomiting in patients with head and neck squamous cell carcinoma (HNSCC) treated with IMRT; these results suggest that radiation dose to the brainstem outside of the target volume influences the incidence of vomiting during IMRT for HNSCC, including nasopharyngeal carcinoma,” they added. [Radiother Oncol 2014;111:281-288; Pract Radiat Oncol 2014;4:267-271; J Radiat Oncol 2013;2:407-412]

In addition, several lines of evidence have shown that neurokinin-1 receptor antagonist (NK-1RA) may play the antiemetic role at the level of the brainstem. [Neurosci Lett 2000;286:123-126; Neuropharmacology 2000;39:316-323; Neurosci Lett 2001;314:102-104]

Safety and quality of life

“The tolerability profile, quality-of-life data, and survival outcomes showed that weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival,” the investigators said.

There were no significant differences between the weekly and every-3-weeks groups in the frequency of adverse events (AEs) or serious AEs (grade ≥3), none of which were attributed to fosaprepitant. None of the patients experienced grade 4 or 5 AEs.

Finally, patients in the weekly group had improved scores for multiple quality-of-life measures compared with those in the every-3 weeks group. There was no significant difference in survival outcomes between the two groups (91.8 percent vs 93.7 percent; p=0.99).

The study included of 100 patients (mean age 46.6 years, 83.0 percent male) who had achieved chemotherapy-induced nausea and vomiting control after induction chemotherapy. These patients were randomly assigned to receive fosaprepitant weekly (50 patients) or every 3 weeks (50 patients) during CCRT.