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Meta-Analysis
. 2025 Sep;21(21):2823-2833.
doi: 10.1080/14796694.2025.2542108. Epub 2025 Aug 9.

Individual patient data meta-analysis of NEPA versus aprepitant-based antiemetic regimens for preventing chemotherapy-induced nausea and vomiting

Rudolph M Navari  1 , Timothy Tyler  2 , Naoki Inui  3 , Hirotoshi Iihara  4 , Erminio Bonizzoni  5 , Yeon Hee Park  6 , Hope S Rugo  7 , Eric J Roeland  8
Affiliations
Meta-Analysis

Individual patient data meta-analysis of NEPA versus aprepitant-based antiemetic regimens for preventing chemotherapy-induced nausea and vomiting

Rudolph M Navari et al. Future Oncol. 2025 Sep.

Abstract

Aim: Because no conclusive data demonstrate superiority among NK1 receptor antagonists (RA), existing antiemetic guidelines regard them as interchangeable. This individual patient data (IPD) meta-analysis compared the efficacy of NEPA (netupitant/fosnetupitant) and aprepitant/fosaprepitant-based regimens in preventing chemotherapy-induced nausea and vomiting (CINV).

Materials & methods: Head-to-head comparative studies published between 2003 and 2022 that evaluated antiemetic prophylaxis of aprepitant or fosaprepitant versus oral or intravenous (IV) NEPA in patients with various cancers receiving highly (HEC) or moderately emetogenic chemotherapy (MEC) were identified through a literature search. We combined individual patient data to assess complete response (no emesis/no rescue medication) and no significant nausea using a two-stage approach.

Results: A total of six studies involving 2,767 patients were included evaluating NEPA plus dexamethasone versus aprepitant/fosaprepitant plus any 5-HT3RA plus dexamethasone for patients with cancer receiving HEC/MEC. Complete response and no significant nausea rates were similar during the acute (0-24 h) phase but NEPA showed significantly higher rates than aprepitant during the delayed ( > 24-120 h) and overall (0-120 h) phases and on Days 3-5 following chemotherapy.

Conclusion: Improved CINV prevention was observed with NEPA-based regimens, particularly during Days 3-5, highlighting its potential for managing prolonged nausea and vomiting associated with emerging anticancer targeted therapies.

Keywords: CINV; NEPA; antiemetic; aprepitant; nausea; netupitant; palonosetron; vomiting.

Plain language summary

This study examined two types of medicine to help cancer patients feel less sick during chemotherapy. Both types try to stop nausea and vomiting. One kind is called NEPA, and the other is called aprepitant. Both include drugs taken by mouth or given through an IV. All patients also took other common medicines to help with side effects. The researchers looked at six studies with a total of 2,767 patients. They wanted to see which medicine worked better. On the first day of chemotherapy, both types worked about the same. But in the days after chemotherapy, NEPA worked better. It helped prevent vomiting and more severe nausea. It also meant fewer people needed extra medicine to feel better. This improvement was true from day 2 to day 5 after treatment. The study shows that NEPA may give better long-term relief from chemotherapy side effects, which may be especially helpful for patients who are using newer cancer drugs that can cause longer-lasting nausea.

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Conflict of interest statement

R. M. Navari reports no competing interests.

T. Tyler reports participating in speaker’s bureaus for BMS, Amgen, Sanofi Genzyme, Incyte, and Pharmacosmos and reports receiving consultancy fees from Pfizer Oncology, AstraZeneca, TerSera, and Sandoz.

N. Inui reports participating in speakers’ bureaus for Chugai Pharmaceutical, Lilly, Nippon Boehringer Ingelheim, Novartis, Taiho Pharmaceutical, AstraZeneca, Takeda Pharmaceutical, Amgen, and Merck and reports receiving research funding from Chugai Pharmaceutical, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, AstraZeneca (Inst), and Kyowa Kirin International.

H. Iihara reports having received personal fees from Astellas Pharma Co., Ltd., AstraZeneca plc, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly and Company, Nippon Kayaku Co., Ltd., Ohara Pharmaceutical Co.,Ltd., Sawai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Yakult Honsha Co., Ltd., outside the submitted work.

E. Bonizzoni reports receiving consultancy fees from Helsinn Healthcare and Zambon Biotech.

Y. H. Park reports receiving grants from MSD, Pfizer, AstraZeneca, Gencurix, Roche, Novartis, and Inocras; receiving consultancy or advisory board fees from AstraZeneca, MSD, Pfizer, Eisai, Lilly, Roche, Gilead, Daiichi-Sankyo, Helsinn MENARINI, Novartis, and EVEREST; receiving manuscript fees from AstraZeneca, Pfizer, Roche, MSD, Daiichi-Sankyo, Novartis, and Gilead; and receiving honoraria from AstraZeneca, MSD, Pfizer, Roche, Daiichi-Sankyo, Novartis, Gilead, and Helsinn. Dr. Park also reports receiving support for attending meetings or for travel from Gilead, Pfizer, and AstraZeneca, and receiving research funding from AstraZeneca, Pfizer, MSD, and Daewoong or for contract research from AstraZeneca, Pfizer, MSD, and Kirin.

H. S. Rugo reports receiving consultancy/advisory fees from Napo, and Helsinn and receiving institutional research support to her former institution (UCSF) from AstraZeneca, Daiichi Sankyo, Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Gilead Sciences, Inc., Lilly; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer, Stemline Therapeutics, and Ambryx.

E. J. Roeland reports being a member of the scientific advisory board for Pfizer, Napo Pharmaceuticals, and Aveo Pharmaceuticals; consultant for Dexcel Pharma, and Ryvu Therapeutics; research funding Napo Pharmaceuticals, Pfizer (all to institution); and expert witness for Heron Therapeutics.

Editorial and medical writing assistance was provided by Jennifer Vanden Burgt, an independent consultant from Minneapolis, MN, and funded by Helsinn Healthcare SA, Lugano, Switzerland.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram.
Figure 2a.
Figure 2a.
Crude pooled daily incidence of breakthrough emesis and/or use of rescue medication (all patients in the intent-to-treat population).
Figure 2b.
Figure 2b.
Crude pooled daily incidence of breakthrough significant nausea (all patients in the intent-to-treat population).
See this image and copyright information in PMC

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