# Safety and antiemetic efficacy of weekly administration of netupitant/palonosetron plus dexamethasone during 5 weeks of concomitant chemo-radiotherapy—the DANGER-emesis study

## TL;DR

This study shows that weekly administration of NEPA plus dexamethasone is safe and effective for preventing nausea and vomiting in cervical cancer patients undergoing chemo-radiotherapy.

## Contribution

The study introduces a simplified weekly antiemetic regimen using NEPA plus dexamethasone for cisplatin-based chemo-radiotherapy.

## Key findings

- Weekly NEPA plus dexamethasone was safe with mostly mild/moderate side effects.
- The regimen prevented vomiting in 86% of patients and nausea in 18% over 35 days.
- Mean time to first emetic episode was 9 days, indicating high efficacy.

## Abstract

Netupitant 300 mg/palonosetron 0.5 mg (NEPA) would be ideal as antiemetic prophylaxis for patients receiving weekly cisplatin, as it would reduce concurrent medication intake compared to the 3-day aprepitant regimen. However, due to the longer half-life of netupitant (~ 88 h), weekly administration could potentially lead to accumulation and toxicity. This study aims to investigate the safety and antiemetic efficacy of weekly administration of NEPA plus dexamethasone (DEX) in patients treated for cervical cancer with radiotherapy and weekly cisplatin 40 mg/m2.

This single-arm, open-label, phase II study evaluated patients with cervical cancer receiving NEPA and DEX before weekly cisplatin and concomitant radiotherapy for up to 5 weeks. Safety was assessed during weekly adverse event (AE) assessments. Efficacy was evaluated using Patient Diaries reporting daily nausea, vomiting, and use of rescue medication during the study period.

Between October 8, 2018, and January 2, 2024, 73 patients were recruited from two Danish departments of oncology; 37 completed all five weekly cycles. The majority of AEs were of mild or moderate intensity, with fatigue being the most frequently observed (95% of patients). Seven (10%) patients encountered ≥ 1 grade 3 treatment-related AEs (TRAEs). No grade 4 TRAEs or deaths were observed. In terms of efficacy, no vomiting and no nausea days 1–35 were 86% and 18%, respectively. Mean time to first emetic episode was 9 days.

Weekly NEPA administration was safe, well-tolerated, and highly effective during concomitant radiotherapy and weekly cisplatin.

This trial is registered at ClinicalTrials.gov (NCT03668639-2018–09-10).

The online version contains supplementary material available at 10.1007/s00520-025-09573-9.