Comparative Efficacy of Fosnetupitant and Fosaprepitant for Delayed Vomiting in Patients Receiving Irinotecan-Oxaliplatin Combination Chemotherapy: A Retrospective Propensity Score-Matched Study

Purpose: Appropriate prevention of chemotherapy-induced nausea and vomiting (CINV) is essential for improving patients’ quality of life; however, no studies have compared neurokinin-1 receptor antagonists in regimens combining oxaliplatin and irinotecan. We aimed to compare the antiemetic efficacy of fosnetupitant and fosaprepitant in patients receiving FOLFIRINOX or FOLFOXIRI regimens. Patients and Methods: We reviewed records of patients receiving FOLFIRINOX or FOLFOXIRI between April 1, 2018 and September 30, 2024 at Tokushima University Hospital. Eligible patients completed the first chemotherapy cycle, received standard triple antiemetic prophylaxis, and had complete nursing-recorded CINV follow-up data for days 1– 7. Patients were matched 1:1 using propensity scores for age, sex, alcohol consumption history, prior treatment, regimen, and chemotherapy doses. The primary objective was to compare the incidence of vomiting during the long-delayed phase (days 6– 7) between the fosnetupitant and fosaprepitant groups. The no-vomiting and no-nausea rates were compared using Fisher’s exact test, and the time to first vomiting using the Log rank test. Results: After matching, data from 68 balanced patient pairs were analyzed. The fosnetupitant group had higher no-vomiting rates in the long-delayed phase (100% vs. 91.2%, p=0.028) and overall period (95.6% vs. 83.8%, p=0.045), compared with the fosaprepitant group. No significant intergroup difference was observed in the overall no-nausea rate (26.5% vs. 32.3%, p=0.573). With fosnetupitant, the time to first vomiting was longer (3/68 vs. 11/68, hazard ratio: 0.20, p=0.045), injection site reactions were fewer (0.0% vs. 19.1%, p< 0.001), and constipation and hiccup incidences were fewer (p> 0.05). Conclusion: Despite the retrospective design, possible calendar-time confounding, and limited number of events, our results suggest that fosnetupitant offers better control of long-delayed and overall vomiting and a favorable safety profile, compared with fosaprepitant, in patients receiving FOLFIRINOX/FOLFOXIRI regimens. Infographic: Fosnetupitant vs. Fosaprepitant for vomiting prevention in FOLFIRINOX/FOLFOXIRI patients.Patients receiving FOLFIRINOX or FOLFOXIRI are shown. Propensity score-matched pairs (68 pairs) compare Fosnetupitant versus Fosaprepitant. Long-delayed vomiting (Days 6-7) results show 100 percent no vomiting with Fosnetupitant and 91.2 percent no vomiting with Fosaprepitant. The hazard ratio (HR) is 0.20 (0.05-0.56), Firth corrected. Firth’s penalized Cox regression analysis is mentioned.