Phase II Clinical Trial of NEPA (Netupitant/Palonosetron) for Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) in Patient Receiving the BEAM Conditioning Regimen

Abstract

The management of chemotherapy-induced nausea and vomiting (CINV) during preparative regimens for Hematopoietic Stem Cell Transplant (HSCT) continues to be a poorly studied area and an unmet patient need. The primary aim of this study was to assess the efficacy of NEPA to prevent N/V both during and after HSCT conditioning. NEPA is a recently approved combination antiemetic, containing fixed doses of netupitant and palonosetron. Nausea, emesis, and nutritional intake, were evaluated from the start of conditioning through day 4 post-transplant. NEPA was administered Days 1, 3 and 6 of conditioning, dexamethasone (Days 1-6) and BEAM (Carmustine (300 mg/m2 D1), Etoposide/Cytarabine (200/400 mg/m2 D2-5), Melphalan (140 mg/m2 D 6)) preparative regimen (Days 1-6) in 17 patients. Patient nausea and emesis was self-reported using daily assessments and rescue therapy was determined using chart review. Two out of 17 patients experienced emesis (11.7%) after all chemotherapy was completed with no emesis in any patient during chemotherapy. During the observation period, 6 patients did not receive rescue medications (35%) and time to first rescue in other patients was a mean of 188.9 hours from the start of chemotherapy (median 172.4, SD 89 hrs). Responses were classified as either complete (CR) or major (MR), with CR defined as: no emesis, mild-moderate nausea for hours 0-264 (6 days of chemotherapy and 5 days post-chemotherapy), and (MR) defined as: 1-2 emesis on only 1 day with any level nausea or no emesis with severe nausea. Five out of 16 patients reported CR (31%) and 11 reported a major response (69%) at their end of treatment (EOT) visit. One patient did not participate in the EOT visit. The patient population in this study was 47% female, 100% Caucasian, the average age was 62 years old and the following diagnoses were included: Peripheral T-cell Lymphoma (24%), Hodgkin lymphoma (23%), mantle cell lymphoma (29%), and Diffuse large B-cell lymphoma (24%). The following expected adverse events were reported amongst 17 treated patients: anemia (82%); neutropenia (65%); lymphocyte decrease (94%); decreased neutrophils (94%); white blood cell decrease (88%); abdominal pain (59%); constipation (53%); diarrhea (59%); abdominal cramping (35%); nausea (82% all grades); bacteremia (29%); hypophosphatemia (24%); and hypokalemia (29%). Constipation was deemed possibly related to NEPA; additional reported adverse events were not related to study drug. In this interim analysis, NEPA plus dexamethasone was effective in preventing emesis with BEAM conditioning with no increase in adverse events prior to HSCT.