A Prospective Non-Randomized Observational Study assessing efficacy of Netupitant and Palonosetron (NEPA) Versus Fosaprepitant and Palonosetron for Chemotherapy Induced Nausea and Vomiting Prevention in Autologous Stem Cell Transplantation at a South Indi
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Abstract
Background: Chemotherapy-induced nausea and vomiting remain a significant problem during autologous stem cell transplantation, particularly during the delayed period of conditioning regimen chemotherapy. NEPA (netupitant+palonosetron) offers dual NK1/5-HT3 blockade in a single dose, but comparative evidence versus fosaprepitant+palonosetron in Autologous stem cell transplantation is limited.
Methods: We conducted a prospective, observational, non-randomized study at a tertiary cancer centre (September 2022–January 2025). Consecutive Transplant recipients received either BEAM (lymphoma) or melphalan (myeloma) conditioning. Antiemetic prophylaxis was NEPA (netupitant 300mg + palonosetron 0.5 mg) or fosaprepitant 150mg + palonosetron 0.25 mg. Vomiting episodes and CTCAE v4 grades were recorded daily. Acute (0–24 h), delayed (24–120 h), and overall (0–120 h) outcomes were analysed using Mann–Whitney and Chi-square tests.
Results: Sixty-five patients were included in the study (median age 42 years, with range 16–65; 60% male). Myeloma accounted for 34 (52.3%) and lymphoma 31 (47.7%). Antiemetic allocation was fosaprepitant+palonosetron in 43 (66.2%) and NEPA in 22 (33.8%), driven by affordability and availability.
Conditioning comparison: Acute outcomes were similar for BEAM versus melphalan (episodes 0.61 ± 1.54 versus 0.44 ± 0.93, p=0.828). In the delayed phase, BEAM showed a trend toward higher emesis (episodes 4.23 ± 4.30 versus 2.94 ± 4.57, p=0.105), with significantly higher vomiting grade on day 3 (p=0.042).
Antiemetic comparison: Acute, delayed, and overall summaries did not differ significantly between NEPA and fosaprepitant+palonosetron. On delayed day 5, NEPA was superior, with fewer episodes (0.32 ± 0.65 versus 0.88 ± 1.12; p=0.040) and lower vomiting grade (0.23 ± 0.43 versus 0.56 ± 0.67; p=0.047). No other day-wise differences were significant.
Conclusions: In this real-world Autologous stem cell transplantation cohort, NEPA and fosaprepitant+palonosetron achieved comparable overall control. NEPA conferred a distinct late delayed (day 5) benefit, while BEAM conditioning was associated with higher delayed vomiting grades than melphalan. NEPA may be preferred when late-phase control is critical. Larger randomized trials stratified by conditioning regimen are warranted.
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References
2. Zhang H, Zeng Q, Dong T, et al. Comparison of netupitant/palonosetron with 5-hydroxytryptamine-3 receptor antagonist in preventing chemotherapy-induced nausea and vomiting in patients undergoing hematopoietic stem cell transplantation. Front Oncol. 2023;13:1280336. doi:10.3389/fonc.2023.1280336
3. National Comprehensive Cancer Network. Antiemesis (Version 2.2025). NCCN Clinical Practice Guidelines in Oncology. Published 2025.
4. Roila F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(suppl 5):v119-v133. doi:10.1093/annonc/mdw270
5. Aapro M, Rugo H, Rossi G, et al. A randomized phase III study evaluating NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting. Ann Oncol. 2014;25(7):1340-1346. doi:10.1093/annonc/mdu116
6. Navari RM. Prevention of emesis from multiple-day and high-dose chemotherapy regimens. J Natl Compr Canc Netw. 2007;5(1):51-59. doi:10.6004/jnccn.2007.0006
7. Saad A, Taneja A, Di Stasi A, et al. Impact of high-dose steroid premedication on the outcome of myeloablative T-cell replete haploidentical peripheral blood stem cell transplant. Bone Marrow Transplant. 2018;53(10):1345-1348. doi:10.1038/s41409-018-0185-2
8. National Comprehensive Cancer Network. Antiemesis (Version 2.2022). NCCN Clinical Practice Guidelines in Oncology. Published 2022. Plymouth Meeting, PA.
9. Zelek L, Debourdeau P, Bourgeois H, et al. A pragmatic study evaluating NEPA versus aprepitant for prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Oncologist. 2021;26(10):e1870-e1879. doi:10.1002/onco.13881
10. Gralla RJ, Bosnjak SM, Hontsa A, et al. A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. Ann Oncol. 2014;25(7):1333-1339. doi:10.1093/annonc/mdu115
11. Di Renzo N, Musso M, Scimè R, et al. Efficacy and safety of multiple doses of NEPA without dexamethasone in preventing nausea and vomiting induced by multiple-day and high-dose chemotherapy in patients with non-Hodgkin lymphoma undergoing autologous hematopoietic stem cell transplantation: a phase IIa, multicenter study. Bone Marrow Transplant. 2020;55:2114-2120. doi:10. 1038/s41409-020-0909-2
12. Gao A, Guan S, Sun Y, et al. Prolonged usage of fosaprepitant for prevention of delayed chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. BMC Cancer. 2023;23(1):609. doi:10.1186/s12885-023-11066-5
13. Yang Y, Yang N, Wu L, et al. Safety and efficacy of aprepitant as mono and combination therapy for the prevention of emetogenic chemotherapy-induced nausea and vomiting: post-marketing surveillance in China. Chin Clin Oncol. 2020;9:68. doi:10.21037/cco-20-160
14. Schwartzberg LS, McLaughlin T, Geller RB, et al. Real-world efficacy: intravenous palonosetron three-drug regimen for chemotherapy-induced nausea and vomiting with highly emetogenic chemotherapy. J Comp Eff Res. 2018;7:1161-1170. doi:10.2217/cer-2018-0089
15. Dranitsaris G, Molassiotis A, Clemons M, et al. The development of a prediction tool to identify cancer patients at high risk for chemotherapy-induced nausea and vomiting. Ann Oncol. 2017;28:1260-1267. doi:10.1093/annonc/mdx100
16. Spinelli T, Calcagnile S, Giuliano C, et al. Netupitant PET imaging and ADME studies in humans. J Clin Pharmacol. 2014;54(1):97-108. doi:10.1002/jcph.191
17. Rojas C, Raje M, Tsukamoto T, Slusher BS. Molecular mechanisms of 5-HT3 and NK1 receptor antagonists in prevention of emesis. Eur J Pharmacol. 2014;722: 26-37. doi:10.1016/j.ejphar.2013.09.072
18. Stathis M, Pietra C, Rojas C, Slusher BS. Inhibition of substance P–mediated responses in NG108-15 cells by netupitant and palonosetron exhibit synergistic effects. Eur J Pharmacol. 2012;689(1-3):25-30. doi:10.1016/j.ejphar.2012.05.031
19. Thomas AG, Stathis M, Rojas C, Slusher BS. Netupitant and palonosetron trigger NK1 receptor internali-zation in NG108-15 cells. Exp Brain Res. 2014;232 (8):2637-2644. doi:10.1007/s00221-014-3968-y
20. Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008;358(23):2482-2494. doi:10.1056/NEJMra0706547
21. Vidall C, Fernández-Ortega P, Cortinovis D, Jahn P, Amlani B, Scotté F. Impact and management of chemotherapy/radiotherapy-induced nausea and vomiting and the perceptual gap between oncologists/oncology nurses and patients: a cross-sectional multinational survey. Support Care Cancer. 2015;23:3297-3305. doi:10.1007/s00520-015-2750-5
22. Aapro M, Ruffo P, Panteri R, Costa S, Piovesana V. Oncologist perspectives on chemotherapy-induced nausea and vomiting (CINV) management and outcomes: a quantitative market research–based survey. Cancer Rep (Hoboken). 2018;1:e1127. doi:10.1002/cnr2.1127
23. Karthaus M, Oskay-Özcelik G, Wülfing P, et al. Real-world evidence of NEPA, netupitant–palonosetron, in chemotherapy-induced nausea and vomiting prevention: effects on quality of life. Future Oncol. 2020;16:939-953. doi:10.2217/fon-2020-0187