Efficacy and Safety of Oral NEPA (Netupitant/Palonosetron), the First Fixed-Combination Antiemetic, in Patients With Gynecological Cancers Receiving Platinum-Based Chemotherapy.

OBJECTIVE: Patients with gynecological cancers are at high risk for chemotherapy-induced nausea and vomiting (CINV) after platinum-based chemotherapy (CT). NEPA (300-mg netupitant, 0.50-mg palonosetron) is the first oral fixed-combination antiemetic. Pivotal trials demonstrated the superiority of oral NEPA over intravenous palonosetron in preventing CINV after highly emetogenic (anthracycline-cyclophosphamide-based [AC] and cisplatin-based [non-AC]) CT. This post hoc subset analysis considered patients with gynecological cancer receiving cisplatin- or carboplatin-based CT from 1 pivotal trial and from 1 multicycle safety trial to evaluate the efficacy of oral NEPA in preventing CINV. METHODS: Single-dose NEPA was given before CT in combination with dexamethasone. The efficacy end points for the acute (0-24 hours), delayed (25-120 hours), and overall (0-120 hours) CINV phases after CT included complete response (CR; no emesis, no rescue medication) and no significant nausea (<25 mm on a 0- to 100-mm visual analog scale). Safety was also assessed. RESULTS: For cisplatin-induced CINV, NEPA achieved high CR rates (acute phase: >90%; delayed, overall phases: ≥85%). For carboplatin-induced CINV, NEPA was also highly effective, with high acute, delayed, and overall CR rates (cycle 1: >75%; cycles 2-4: >95%). No significant nausea rates were more than 90% and more than 80% in the acute and delayed phases, respectively, for patients receiving cisplatin or carboplatin. NEPA was well tolerated. CONCLUSIONS: Results suggest that oral NEPA is effective and safe in preventing CINV in patients with gynecological cancers treated with cisplatin- or carboplatin-based CT. Single fixed-combination NEPA is a convenient option for CINV prevention in high-risk CINV patients.

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.

PURPOSE: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. METHODS: This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. RESULTS: Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. CONCLUSIONS: NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

Efficacy and safety of oral palonosetron compared with IV palonosetron administered with dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid tumors receiving cisplatin-based highly emetogenic chemotherapy (HEC).

PURPOSE: This study aims to compare the efficacy and safety of oral palonosetron with intravenous (IV) palonosetron for the prevention of cisplatin-related chemotherapy-induced nausea and vomiting (CINV). METHODS: A multinational, randomized, double-blind study enrolling adult chemotherapy-naive patients with malignant solid tumors scheduled to receive cisplatin-based highly emetogenic chemotherapy (HEC). Patients received oral palonosetron (0.50 mg) or IV palonosetron (0.25 mg), each with oral dexamethasone. The primary objective was to demonstrate non-inferiority in terms of patients with a complete response (CR, no emesis/no rescue medication) within the acute phase (0-24 h after chemotherapy administration). RESULTS: Of the 743 patients randomized, 739 received study medications and 738 were included in the full analysis set. The CR rate in the acute phase was high for both groups (oral 89.4 %; IV 86.2 %). As this difference in proportions (stratum-adjusted Cochran-Mantel-Haenszel method) was 3.21 % (99 % confidence interval (CI) -2.74 to 9.17 %), non-inferiority was demonstrated (since the lower limit of the 99 % CI was closer to zero than the predefined margin of 15 %). Treatment-emergent adverse events (TEAEs) related to the study drug were rare (oral 3.2 %; IV 6.5 %). No TEAEs related to study drug leading to discontinuation were reported. CONCLUSION: Non-inferiority of oral versus IV palonosetron was demonstrated. The CR rate in the acute phase was >86 % in both patient groups. The safety profiles were comparable.