Safety of an Oral Fixed Combination of Netupitant and Palonosetron (NEPA): Pooled Data From the Phase II/III Clinical Program

Abstract

Background. Standard prophylaxis for chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK 1 RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA 1 dexamethasone in comparison with current therapies across all phase II/III trials. Materials and Methods. This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA 1 dexamethasone, palonosetron 1 dexamethasone, and aprepitant 1 ondansetron/palonosetron 1 dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures.

A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting

“…A similar frequency of cardiac AEs was reported in each treatment group during all cycles of treatment [ 47 ]. The mean changes from baseline in the ECG parameters assessed (heart rate, PR, QRS, QT, QTcB, and QTcF) were small and generally similar across the treatment groups at each study time point.…”

“…The most frequent treatment-related adverse events were headache and constipation. Aapro et al [ 47 ] presented a comprehensive overview of the safety of NEPA, pooling data from the studies in the development program. The percentages of patients with at least 1 treatment-emergent adverse event (TEAE) in Cycle 1 and in all cycles were generally similar for NEPA, oral palonosetron, and the aprepitant groups as were the percentages of patients reporting AEs considered to be treatment-related ( Table 6 ).…”

Efficacy of osimertinib against EGFRvIII+ glioblastoma

“…While a large body of evidence suggests that EGFR plays a significant role in GBM growth [4][5][6], previous efforts to target this receptor using EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have been unsuccessful [7]. There are two central reasons why these agents may have been ineffective in treating GBM patients:1) all four FDAapproved EGFR-TKIs that have been tested so far in GBM patients (erlotinib [8,9], gefitinib [8,10], lapatinib [11], and afatinib [12]) do not cross the blood-brain barrier effectively; and 2) the extreme molecular and functional heterogeneity of EGFR, as mentioned above, could not be taken into account at the time these clinical trials were performed because this information was not yet understood [13][14][15]. Negative results in previous studies involving EGFR-TKIs in GBM patients can be in part explained by a failure to address the above two requirements.…”

Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy

“…Approval of oral NEPA (netupitant 300 mg and palonosetron 0.50 mg) in the U.S. and Europe was based on studies in which a single oral NEPA capsule plus dexamethasone (DEX), given prior to cisplatin‐ and anthracycline‐cyclophosphamide (AC)‐based chemotherapy, demonstrated superior efficacy in preventing CINV over palonosetron plus DEX for 5 days postchemotherapy . The overall and cardiac safety of oral NEPA was also well established in almost 1,200 NEPA‐treated patients .…”