NEPA, a fixed-dose combination of netupitant and palonosetron, proved more effective than palonosetron alone in preventing chemotherapy-induced nausea and vomiting (CINV) in a large multinational study of 1455 patients, according to data presented at the 2013 San Antonio Breast Cancer Symposium.
Hope S. Rugo, MD, Director of Breast Oncology and Clinical Trials at the Helen Diller Family Comprehensive Cancer Center of the University of California San Francisco, presented the results of a phase 3, randomized, double-blind trial of chemotherapy-naive patients undergoing doxorubicin/cyclophosphamide (AC) chemotherapy.
“Breast cancer patients receiving AC are at significant risk for developing CINV due not only to the emetogenicity of the chemotherapy but also to their young age and gender,” Rugo noted. “As recommended by international antiemetic guidelines, targeting multiple molecular pathways involved in emesis is important for maximizing control of CINV and improving the functional status of breast cancer patients during chemotherapy.”
She pointed out that in patients receiving AC, the guidelines now consistently recommend the prophylactic combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone, but adherence to these guidelines is suboptimal. “Many patients still suffer from CINV, particularly during the delayed phase following chemotherapy,” she indicated.
NEPA is a fixed-dose combination of netupitant (300 mg), a highly selective NK1 receptor antagonist, and the 5-HT3 receptor antagonist palonosetron (0.50 mg), which allows this 1 drug to target dual antiemetic pathways.
“NEPA has been developed to allow patients to receive guideline-based targeted antiemetic prophylaxis in a single, convenient oral dose,” Rugo said.
Randomized Study Details
The study involved 1455 chemotherapy-naive patients (97% with breast cancer) scheduled to receive their first course of AC chemotherapy. They were randomly assigned to receive oral NEPA or oral palonosetron, each with oral dexamethasone 12 mg. The primary end point was complete response (no emesis, no rescue medication) during the delayed (25-120 hours) phase postchemotherapy.
Each patient completed a diary from the start of chemotherapy on day 1 through day 6, capturing the frequency and duration of each emetic episode, severity of nausea, and rescue medications taken. The treatment’s impact on daily living was assessed with the Functional Living Index-Emesis (FLIE) questionnaire.
“NEPA showed superior complete response rates during the acute, delayed, and overall phases following chemotherapy compared with palonosetron. This superior prevention of CINV correlated with a significantly greater proportion of NEPA-treated patients experiencing no impact on daily living as a result of CINV, based on all domains of the FLIE,” Rugo reported. See the Table.
Similarly, NEPA was consistently more effective than palonosetron during the delayed and overall phases for the secondary efficacy end points of no emesis, no significant nausea, and complete protection, as well as during the acute phase for no emesis, she said.
Adverse Events Similar
“NEPA was well tolerated, with a similar safety profile to palonosetron,” Rugo reported.
Overall, the incidence, type, and intensity of treatment-emergent adverse events were comparable between the treatment groups. Among patients reporting these, the majority (85%) indicated these events were mild-to-moderate in intensity. There were no treatment-related adverse events leading to discontinuation and very few (0.7%) severe treatment related adverse events for NEPA-treated patients, and none were serious. There was also no evidence of any cardiac safety concerns for either drug, Rugo reported.
She concluded that as a fixed single-dose, guideline-recommended, convenient antiemetic drug combination, “NEPA offers improved efficacy and reduced interference with daily functioning” over palonosetron alone.
Rugo HS, Rossi G, Rizzi G, et al. NEPA, a fixed-dose combination of netupitant and palonosetron, prevents chemotherapy-induced nausea and vomiting (CINV) more effectively and reduces the impact on daily living for breast cancer patients compared with palonosetron. Presented at: San Antonio Breast Cancer Symposium; December 12, 2013; San Antonio, TX. Poster P3-09-01.