Fosnetupitant Versus Fosaprepitant for Delayed Vomiting Upon Irinotecan–Oxaliplatin Combination Chemotherapy for Pancreatic/Colorectal Cancer

Background/Aim: Real-world comparative data on neurokinin-1 receptor antagonists are needed among patients receiving FOLFOXIRI or FOLFIRINOX. We aimed to evaluate the antiemetic effectiveness of fosnetupitant versus that of fosaprepitant in patients treated with FOLFOXIRI/FOLFIRINOX regimens for pancreatic/colorectal cancer.

Patients and Methods: This single-center retrospective study included patients treated from April 2018 to September 2024. Patients were matched 1:1 between treatment groups via propensity scores based on age, sex, alcohol history, prior treatment, and regimen dose, as appropriate. Antiemetic effectiveness was assessed as no vomiting/no nausea during days 1-7; safety outcomes were also evaluated. Inverse probability of treatment weighting (IPTW) was conducted to validate the robustness of the results. Between-group comparisons were performed using Fisher’s exact tests for categorical variables and Mann–Whitney U-tests for continuous variables.

Results: After matching, 43 patient pairs in the pancreatic cancer cohort and 28 pairs in the colorectal cancer cohort were analyzed; the groups had generally comparable baseline characteristics. In the pancreatic cancer cohort, fosnetupitant was associated with higher no-vomiting rates during the long-delayed phase (100% vs. 81%, p=0.006) and overall period (95% vs. 74%, p=0.014) than fosaprepitant. No significant differences in effectiveness were observed in the colorectal cancer cohort. Injection site reactions were significantly less frequent with fosnetupitant in the colorectal cancer cohort (4% vs. 29%, p=0.025). These findings remained consistent in the IPTW sensitivity analysis.

Conclusion: The effectiveness of fosnetupitant may vary according to cancer type, suggesting the need to tailor antiemetic strategies for patients receiving irinotecan–oxaliplatin combination chemotherapy.