NEPA Demonstrates Superiority Over Palonosetron Alone for CINV

NEPA, a treatment intended to control chemotherapy-induced nausea and vomiting (CINV) that combines netupitant and palonosetron, demonstrated superior activity in complete response rates (from 0 to 120 hours) over oral palonosetron monotherapy, according to data presented late June, 2014 at the MASCC/ISOO International Symposium on Supportive Care in Cancer.

NEPA was also superior in preventing emesis, and significant nausea, according to lead study author Matti Aapro, MD, from the department of oncology, Clinique de Genolier, Genolier, Switzerland.

During his presentation Aapro highlighted the importance of the current antiemetic guidelines, which recommend co-administration of targeted prophylactic medications that are designed to inhibit multiple molecular pathways involved in emesis.

He noted that often clinicians are not judicious about following these guidelines, and suggested that simplifying the approach to therapy with the NEPA combination, administered orally in a single capsule, once per cycle (× 4 cycles), could lead to better adherence to the current antiemetic guidelines.

Aapro suggested that NEPA treatment further simplifies the antiemesis prophylaxis by eliminating the need for corticosteroids on Days 2 and 3. He described the evidence supporting the use of NEPA, which comes from 3 previous studies, including a dose-finding study, and two phase III studies, which established the superiority of NEPA over palonosetron after a single chemotherapy cycle. 

The current study was a continuation of the registration study that focused on cycle 1 only. The goal of this study was to determine whether or not patients would continue to benefit from the NEPA prophylaxis in subsequent cycles of therapy. 

This multinational double-blinded phase III study compared the safety and efficacy of a single dose of NEPA compared with oral palonosetron in patients who were chemotherapy naïve and who were receiving multiple cycles of moderately emetogenic chemotherapy (MEC) consisting of an anthracycline and cyclophosphamide.

Oral dexamethasone was administered only on Day 1. The efficacy endpoints assessed included complete response (CR), defined as no emesis/no rescue and no significant nausea with  a maximum less that 25 mm on 100 mm visual analog scale (VAS) during the overall (0—120 h) interval.  

A total of 1455 patients were randomized for the first cycle and 1286 patients for the second and subsequent cycles (multiple cycle extension); a total of 5969 chemotherapy cycles were administered and 76% of the patients had 4 cycles. The treatment arms were well balanced with respect to demographics.  

Continued benefit of NEPA with dexamethasone over palonosetron through cycles 1, 2, 3, and 4 were seen, according Aapro, with all differences showing statistical significance. The results for nausea and emesis were also statistically significant in favor of the NEPA combination and dexamethasone over palonosetron and dexamethasone.

Treatment-related adverse events were rare, and there was no clear difference seen between the arms in terms of the types of adverse events observed in the study. Importantly, as Aapro noted, many clinicians often ask about potential interactions between treatments, and there was no indication of increased neutropenia observed with the combination of NEPA and dexamethasone. 

Aapro M, Karthaus M, Schwartzberg L, et al. Multiple Cycle CINV Control and Safety of NEPA, A Capsule Containing Netupitant and Palonosetron Administered Once per Cycle of Moderately Emetogenic Chemotherapy (MEC). Presented at MASCC/ISOO International Symposium on Supportive Care in Cancer. June 26, 2014. Abstract MASCC-0160