Acknowledgments During the peer review process, the manufacturer of netupitant/palonosetron was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.DeclarationsFunding The preparation of this review was not supported by any external funding.Authorship and Conflict of interest M. Shirley is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content. Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability Not applicable. Additional information about this Adis Drug Review can be found here. AbstractNetupitant/palonosetron (NEPA; Akynzeo®), available in oral and intravenous (IV) formulations, is a fixed-dose combination of the neurokinin 1 (NK1) receptor antagonist netupitant (or the prodrug, fosnetupitant, in the IV formulation) and the second-generation serotonin 3 (5‑HT3) receptor antagonist palonosetron. Administered as a single dose, (fos)netupitant/palonosetron (in combination with dexamethasone) is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in adults. In clinical trials, (fos)netupitant/palonosetron plus dexamethasone was associated with high complete response rates (no emesis and no rescue medication) in the acute, delayed and overall phases in patients receiving highly or moderately emetogenic chemotherapy, with efficacy maintained over multiple cycles. Further, oral netupitant/palonosetron was found to be superior to palonosetron and non-inferior to aprepitant plus granisetron in preventing CINV in individual trials. Both the oral and IV formulations of the drug combination are well tolerated. The fixed-dose combination is concordant with guideline recommendations and provides a simple and convenient option for prophylaxis against acute and delayed CINV in patients receiving highly or moderately emetogenic chemotherapy.© Springer Nature Switzerland AG 2021