Netupitant‐palonosetron combo prevents chemo-induced nausea, vomiting
A fixed single‐dose of netupitant 300 mg plus palonosetron 0.50 mg (NEPA) was better than palonosetron and aprepitant in preventing acute and delayed* chemotherapy-induced nausea and vomiting (CINV) following multiple chemotherapy cycles, according to the results of two phase III trials.
“Oral NEPA [is] the first antiemetic combination agent targeting two critical emetic pathways. [Our findings] demonstrated the superiority [of NEPA] over palonosetron in terms of complete response (CR)** … [and] no significant nausea (NSN) rates during the acute and delayed phases … regardless of whether patients were receiving anthracycline‐cyclophosphamide (AC) MEC***, non‐AC MEC, or HEC*** regimen,” said the researchers.
Subjects were chemotherapy‐naïve patients who had either AC-based chemotherapy (study 1 [S1], n=1,450; median age 54 years, 98.1 percent female) or MEC/HEC (study 2 [S2], n=412; median age 58 years, 50 percent female). S1 participants were randomized 1:1 to receive NEPA or palonosetron; S2 participants were randomized 3:1 to receive NEPA or palonosetron and oral aprepitant 125 mg (day 1) followed by 80 mg (days 2–3). [Cancer Med 2019;8:2064-2073]
In S1, NEPA effectively prevented acute and delayed CINV across four chemotherapy cycles as reflected by the higher overall CR rates vs palonosetron, which ranged from 74–84 percent vs 67–75 percent (p<0.001 for all). The use of NEPA also generated better overall rates of no emesis (80–88 percent vs 72–80 percent; p<0.001 for all) and NSN (75–80 percent vs 69–75 percent; p<0.05 for all) than palonosetron.
NEPA also fared better than aprepitant‐palonosetron in S2 with numerically higher overall CR (81–91 percent vs 76–88 percent) and NSN rates (84–92 percent vs 81–86 percent).
“The high NSN rates are notable given the unmet clinical need for CINV prevention in the delayed setting, particularly for nausea control,” noted the researchers. [Curr Opin Support Palliat Care 2016;10:180-188]
CINV is a debilitating complication of routine chemotherapy which can impair quality of life and compromise treatment adherence if poorly controlled. [Support Care Cancer 2007;15:497-503; N Engl J Med 2008;358:2482-2494] Proper CINV control could subsequently lead to prolonged survival. [J Clin Oncol 2016;34:557-565; JAMA 2017;318:197-198]
“For effective antiemetic prophylaxis … prevention of CINV from the first cycle therefore remains the main goal for successful CINV control,” said the researchers. Moreover, preservation of the antiemetic effect of NEPA over multiple cycles suggests the utility of this combination in providing sustained CINV control beyond the first cycle, they added.
The study also addressed the issue of compliance given the complicated antiemetic schedules which often lead to dosing errors (ie, wrong/missed doses). [Cancer Rep 2018;1:e1127] “The convenient … once‐per‐cycle administration of oral NEPA may improve adherence to antiemetic guidelines and increase treatment compliance, hence improve CINV prevention,” said the researchers, who called for further prospective trials to elucidate the findings.
An intravenous (IV) formulation of NEPA has been developed to offer further convenience, noted the researchers. The US Food and Drug Administration also recently approved the IV NEPA-dexamethasone combo for CINV prevention in chemotherapy including, but not limited to, HEC, they added. “A phase IIIb study evaluating the safety of IV NEPA in AC‐based chemo is underway.”