Nausea and vomiting are common, distressing side effects associated with chemotherapeutic regimens, resulting in reduced quality of life and treatment adherence. Appropriate antiemetic prophylaxis strategies may reduce/prevent chemotherapy-induced nausea and vomiting (CINV). Historically, investigators assessed antiemetics up to 120 hours after chemotherapy. However, CINV can extend beyond this time. Thus, the effect of antiemetics during the long-delayed period (>120 hours) requires investigation. Emerging treatment options, including certain antibody-drug conjugates (ADCs), are associated with high rates of acute and late-onset nausea and vomiting that can last for extended duration. With the increasing number of ADCs approved and in development, there is urgency to control nausea and vomiting in patients receiving these new therapies. In this narrative review, we present the emetogenic potential of ADCs and CINV in the long-delayed period along with antiemetic prophylaxis strategies used to date. We also discuss the promising role of the fixed-combination antiemetic NEPA ([fos]netupitant plus palonosetron) in controlling long-delayed nausea and vomiting, addressing characteristics that may contribute to its longer efficacy duration compared to other antiemetics. Finally, we highlight encouraging results with NEPA in patients receiving the ADCs trastuzumab deruxtecan or sacituzumab govitecan, which suggest NEPA may be an effective antiemetic prophylaxis in these settings.
Keywords: NEPA; Nausea and vomiting; antibody-drug conjugates; antiemetics; long-delayed CINV; netupitant and palonosetron.
Patients with cancer who are treated with chemotherapy often have nausea and vomiting as side effects. These symptoms can be very uncomfortable, negatively impact the quality of life, and may cause patients to stop treatment. Using the right antinausea and vomiting medications can help to reduce symptoms and enable patients to stay on therapy.Many studies have looked at how effective different combinations and doses of these medications are in reducing or preventing nausea and vomiting in the 5 days after chemotherapy treatment. However, it is now clear that nausea and vomiting can last longer than this time period. Newer treatments called antibody-drug conjugates (ADCs) are being used to treat patients with cancer but may also cause nausea and vomiting after 5 days (known as long-delayed nausea and vomiting). To make sure patients receive the best possible care to prevent these symptoms, it is important to understand how well antinausea and vomiting medications work over longer periods of time.This paper discusses how often this long-delayed nausea and vomiting occurs in patients after they have received chemotherapy or ADCs. We also look at different medications that are being used to prevent nausea and vomiting, including a drug called NEPA (netupitant and palonosetron). NEPA is a combination of two antinausea and vomiting medications. It may be a good option for preventing long-delayed nausea and vomiting, as it is effective over longer time periods than other similar medications. NEPA has shown very promising results in studies so far.