Netupitant/palonosetron combination in prevention of chemotherapy-induced nausea and vomiting in patients with bladder cancer

Introduction. Chemotherapy-induced nausea and vomiting remain among the most unpleasant and dangerous side effects. Netupitant/palonosetron (Akynzeo) is an effective and convenient combination therapy for the prevention of nausea and vomiting in patients receiving chemotherapy with moderate to high emetogenic potential.

Aim. To evaluate the efficacy of clinically used regimens for the prevention of nausea and vomiting associated with highly emetogenic antitumor chemotherapy for bladder cancer (netupitant/palonosetron and aprepitant/ondansetron).

Materials and methods. We prospectively analyzed the experience of concomitant antiemetic therapy in 47 patients receiving gemcitabine-cisplatin antitumor chemotherapy for urothelial carcinoma of the bladder. Response rates were calculated in the acute (0–24 h), delayed (24–120 h), and overall phases of the first GC cycle.

Results and discussion. Complete response rates with oral netupitant/palonosetron and aprepitant/ondansetron were 86.9% and 87.5% in the acute (p = 0.2), 82.6% and 75.0% in the delayed (p = 0.02), and 78.3% and 70.8% in the overall (p = 0.04) phases, respectively. Breakthrough vomiting within 120 hours after cisplatin administration occurred in 17.4% of patients in the netupitant/palonosetron group and 20.8% in the aprepitant/ondansetron group (p = 0.25). All cases of breakthrough vomiting developed between days 3 and 5. The incidence of adverse events (AEs) was comparable between the netupitant/palonosetron (65.1%) and aprepitant/ondansetron (62.3%) groups. Most patients (95.7%) rated their AEs as mild to moderate. There were no deaths during the follow-up period. Despite the small sample size, our results are consistent with the current literature data.

Conclusions. Netupitant/palonosetron is highly effective in the prevention of chemotherapy-induced nausea and vomiting. Its oral administration and single dose make it unique, distinguishing it from more complex previous-generation antiemetic therapy regimens. Modern antiemetic prophylaxis can improve the quality of life of most patients; however, further study of the problem of chemotherapy-induced nausea and vomiting is needed.

1. Weir HK, Thompson TD, Stewart SL, White MC. Cancer Incidence Projections in the United States Between 2015 and 2050. Prev Chronic Dis. 2021;18:210006. https://doi.org/10.5888/pcd18.210006.

2. Каприн АД, Старинский ВВ, Шахзадова АО (ред.). Злокачественные новообразования в России в 2024 году (заболеваемость и смертность). М.; 2025. 178 с.

3. Rumyantsev AA, Bulychkin PV, Volkova MI, Gladkov OA, Zukov RA, Matveev VB, Nosov DA. Bladder cancer. Malignant Tumours. 2024;14(3s2):221–241. (In Russ.) https://doi.org/10.18027/2224-5057-2024-14-3s2-1.2-09.

4. Gritskevich AA, Baitman ТР, Mishugin SV, Popov AYu, Oganyan VA, Rusakov IG, Kostin AA. Atezolizumab (Tecentriq) as first-line therapy in patients with metastatic urothelial carcinoma. Meditsinskiy Sovet. 2022;16(22):58–64. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-22-58-64.

5. Kedrova AG, Berishvili AI. Netupitant/palonosetron (NEPA; Akynzeo®) combination in prevention of the nausea and vomiting in patients with breast cancer receiving anthracyclinbased chemotherapy. Opuholi Zenskoj Reproduktivnoj Sistemy. 2023;19(3):54–62. (In Russ.) https://doi.org/10.17650/1994-4098-2023-19-3-54-62.

6. Bagrova SG, Artamonova EV. Akinzeo: a simple solution to a complex problem (a new highly effective strategy for combined antiemetic therapy). Pharmacology & Pharmacotherapy. 2023;(2):50–60. (In Russ.) Available at: https://pmp-agency.ru/tpost/vfo25bi2o1-akinzeo-prostoe-reshenie-slozhnoi-proble.

7. Vaid AK, Gupta S, Doval DC, Agarwal S, Nag S, Patil P et al. Expert Consensus on Effective Management of Chemotherapy-Induced Nausea and Vomiting: An Indian Perspective. Front Oncol. 2020;10:400. https://doi.org/10.3389/fonc.2020.00400.

8. Gupta S, Mv C, Thomas B, Biswas G, Gupta S, Dattatreya PS et al. An Open-Label, Single-Arm, Multicenter, Observational Study Evaluating the Safety and Effectiveness of Akynzeo® in the Management of Chemotherapy-Induced Nausea and Vomiting in India. Cureus. 2024;16(3):e56447. https://doi.org/10.7759/cureus.56447.

9. Aapro M. CINV: still troubling patients after all these years. Support Care Cancer. 2018;26(Suppl. 1):5–9. https://doi.org/10.1007/s00520-018-4131-3.

10. Vaswani B, Dattatreya PS, Bhagat S, Patil S, Barkate H. The effectiveness of NEPA in the prevention of chemotherapy-induced nausea vomiting among chemo naive patients in an Indian setting. BMC Cancer. 2021;21(1):601. https://doi.org/10.1186/s12885-021-08342-1.

11. Aapro M, Karthaus M, Schwartzberg L, Bondarenko I, Sarosiek T, Oprean C et al. NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron. Support Care Cancer. 2017;25(4):1127–1135. https://doi.org/10.1007/s00520-016-3502-x.

12. Molassiotis A, Jordan K, Karthaus M, Dranitsaris G, Roeland EJ, Schwartzberg L et al. Personalised Antiemetic Prophylaxis with NEPA for Patients at High-Risk of Chemotherapy-induced Nausea and Vomiting Receiving Moderately Emetogenic Chemotherapy: Results from the Randomised, Multinational MyRisk Trial. Ann Oncol. 2025:S0923-7534(25)04964-6. https://doi.org/10.1016/j.annonc.2025.10.017.

13. Yang C, Xu P, Wu T, Fan Y, Li Q, Zhang J et al. Safety assessment of neurokinin-1 receptor antagonist: real-world adverse event analysis from the FAERS database. Front Pharmacol. 2024;15:1413709. https://doi.org/10.3389/fphar.2024.1413709.

14. Scotté F, Schwartzberg L, Iihara H, Aapro M, Gralla R, Hesketh PJ et al. 2023 updated MASCC/ESMO Consensus recommendations: Prevention of nausea and vomiting following moderately emetic risk antineoplastic agents. Support Care Cancer. 2023;32(1):45. https://doi.org/10.1007/s00520-023-08222-3.

15. Vladimirova LYu, Gladkov OA, Koroleva IA, Rumyantsev AA, Semiglazova TYu, Tryakin AA et al. Nausea and vomiting. Malignant Tumors. 2024;14(3s2):32–47. (In Russ.) https://doi.org/10.18027/2224-5057-2024-14-3s2-2-02.

16. Zhang L, Lu S, Feng J, Dechaphunkul A, Chang J, Wang D et al. A randomized phase III study evaluating the efficacy of single-dose NEPA, a fixed antiemetic combination of netupitant and palonosetron, versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). Ann Oncol. 2018;29(2):452–458. https://doi.org/10.1093/annonc/mdx698.

17. Chang J, Chen G, Wang D, Wang G, Lu S, Feng J et al. Efficacy of NEPA, a fixed antiemetic combination of netupitant and palonosetron, vs a 3-day aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese patients receiving highly emetogenic chemotherapy (HEC) in a randomized Phase 3 study. Cancer Med. 2020;9(14):5134–5142. https://doi.org/10.1002/cam4.3123.

18. Prasad Singh M, Prakash Gurunthalingam M, Katiyara V, Kambley S. Efficacy of Netupitant–Palonosetron Combination Therapy Compared to Aprepitant-Based Regimens for Chemotherapy-Induced Nausea and Vomiting: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis. Indian J Gynecol Oncolog. 2025;23:61. https://doi.org/10.1007/s40944-025-00991-5.

19. Luo WT, Chang CL, Huang TW, Gautama MSN. Comparative effectiveness of netupitant-palonosetron plus dexamethasone versus aprepitant-based regimens in mitigating chemotherapy-induced nausea and vomiting: a meta-analysis of randomized controlled trials. Oncologist. 2025;30(2):oyae233. https://doi.org/10.1093/oncolo/oyae233.

20. Navari RM, Tyler T, Inui N, Iihara H, Bonizzoni E, Park YH et al. Individual patient data meta-analysis of NEPA versus aprepitant-based antiemetic regimens for preventing chemotherapy-induced nausea and vomiting. Future Oncol. 2025;21(21):2823–2833. https://doi.org/10.1080/14796694.2025.2542108.

21. Aapro M, Iihara H, Olivari Tilola S, Bernareggi А. Model-predicted Neurokinin-1 (NK1) receptor occupancy of netupitant versus aprepitant over an extended time period: implications for controlling nausea and vomiting associated with Antibody-Drug Conjugates (ADCs). Clin Cancer Res. 2025;31(12 Suppl.):P1-04-03. https://doi.org/10.1158/1557-3265.SABCS24-P1-04-03.

22. Eliasen A, Dalhoff K, Mathiasen R, Schmiegelow K, Rechnitzer C, Schelde AB et al. Pharmacogenetics of antiemetics for chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2020;149:102939. https://doi.org/10.1016/j.critrevonc.2020.102939.

23. Eliasen A, Kornholt J, Mathiasen R, Wadt K, Stoltze U, Brok J et al. Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients: A genetic association study. Pharmacogenet Genomics. 2022;32(2):72–78. https://doi.org/10.1097/FPC.0000000000000460.

24. Tsuji D, Matsumoto M, Kawasaki Y, Kim YL, Yamamoto K, Nakamichi H et al. Analysis of pharmacogenomic factors for chemotherapy-induced nausea and vomiting in patients with breast cancer receiving doxorubicin and cyclophosphamide chemotherapy. Cancer Chemother Pharmacol. 2021;87(1):73–83. https://doi.org/10.1007/s00280-020-04177-y.

25. Ghorbani M, Namazi S, Dehghani M, Razi F, Khalvati B, Dehshahri A. Gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the neurokinin-1 receptor antagonist-based antiemetic regimens: A candidate-gene association study in breast cancer patients. Cancer Chemother Pharmacol. 2024;94(2):237–250. https://doi.org/10.1007/s00280-024-04661-9.

26. Yeo W, Mo FKF, Huang J, Yeo HL, Ko WH, Li LV et al. Personalized Prophylactic Antiemetic Regimens for Control of Chemotherapy-Induced Nausea and Vomiting by Pharmacogenetic Analysis of Three Receptor Genes: HTR3A, HTR3B, TACR1. JCO Precis Oncol. 2025;9:e2400858. https://doi.org/10.1200/PO-24-00858.