Efficacy and Safety of Oral NEPA Versus Fosaprepitant Plus Palonosetron for Preventing Chemotherapy-Induced Nausea and Vomiting in Patients with Nasopharyngeal Carcinoma: A Propensity-Score-Matched Retrospective Study

Objectives: This study compared the efficacy and safety of a single oral dose of a fixed-dose combination of netupitant and palonosetron (NEPA) with an intravenous regimen of fosaprepitant (FosAPR, 150 mg) plus palonosetron (PALO, 0.25 mg) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This single-center retrospective cohort study included patients with stage III–IVa NPC who received cisplatin-based induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) from January 2020 to October 2025. Propensity score matching (PSM) generated 214 patients per group. All patients also received olanzapine and dexamethasone. Complete response (CR, defined as no emesis and no rescue medication), nausea control, adverse events, and nutritional status changes were assessed across the acute, delayed, overall, and extended (0–168 h) phases. Results: After PSM, 214 patients were included in each group. During the first IC cycle, the oral NEPA group achieved a higher CR rate in the extended overall phase (0–168 h) than the FosAPR + PALO group (80.0% vs. 70.1%, p = 0.019). A similar difference was seen in the first CCRT cycle (74.8% vs. 64.5%, p = 0.021). The advantage persisted across subsequent cycles, with no between-group difference in the acute phase. Nausea control also favored oral NEPA: rates of no significant nausea (visual analog scale < 25 mm) during the extended overall phase were 77.1% versus 65.9% in the first IC cycle (p= 0.010) and 72.9% versus 60.3% in the first CCRT cycle (p = 0.006). Fewer patients in the NEPA group required rescue antiemetics (14.5% vs. 22.0% in the first IC cycle, p = 0.045), and the median time to first rescue was longer (58.3 vs. 51.3 h, p < 0.001). Adverse event profiles were similar between groups, with constipation being the most common. Nutritional outcomes, including weight loss ≥ 5% and severe malnutrition, did not differ significantly. Conclusions: For patients with LA-NPC receiving highly emetogenic chemotherapy (HEC), oral NEPA appears to offer superior and sustained chemotherapy-induced nausea and vomiting (CINV) prophylaxi with a simplified administration schedule compared with the intravenous FosAPR plus PALO regimen. These findings warrant confirmation in prospective studies.