The combination of palonosetron (PAL), aprepitant (APR) and dexamethasone (DEX) is the standard regimen in controlling highly emetogenic chemotherapy-induced nausea and vomiting (HEC CINV) in cancer patients. We previously demonstrated that ramosetron (RAM), 5-HT3 receptor antagonist, is superior to ondansetron. This prospective, multicenter, single blind, randomized and phase IV study compares RAM, APR and DEX (RAD) with PAL, APR and DEX (PAD) to prove the non-inferiority of RAD in controlling HEC CINV.
Patients were randomly assigned at 1:1 ratio to receive either RAD or PAD regimen: RAM(0.3mg IV) or PAL(0.25mg IV), D1 in combination with APR(125mg PO, D1 and 80mg PO, D2-3) and DEX(12 mg PO or IV, D1 and 8 mg PO, D2-4). They were stratified by gender, chemotherapy (cisplatin vs non-cisplatin) and administration schedule (single vs multi-day). The primary endpoint, overall complete response (CR) was defined as no emesis and no rescue regimen within 5 days of HEC. The secondary endpoints were overall complete protection (CP: CR + nausea score<25mm) and total control (TC: CR + nausea score<5mm). Quality of life (QOL) was assessed by Functional Living Index–Emesis (FLIE) questionnaire on D0 and D6.
A total of 279 patients receiving RAD (n = 137) or PAD (n = 142) were evaluated for the efficacy and safety. The overall CR rates of RAD vs PAD were 72.3% vs 74.6% (relative difference [RD] -2.4%, 95% CI: -12.8 to 8.0), respectively. The overall CP and TC rates in RAD vs PAD were 52.6% vs 57.0%(RD -4.5%, 95% CI: -16.2 to 7.2) and 45.3% vs 43.0%(RD 2.3%, 95% CI: -9.4 to 14.0%), respectively. FLIE score≥108 (no impact of daily life) was comparable between RAD (n = 134) and PAD (n = 139) (73.9% vs 73.4%, p = 1.00 respectively). Each nausea and vomiting domain (FLIE score≥ 54) was 67.2% vs 64.0 %(p = 0.61) and 91.8% vs 90.6 %(p = 0.83), respectively. The adverse events were similar between the two groups.
In all aspects of the efficacy, safety and QOL, our data suggested RAD was comparable to PAD for the control of CINV in cancer patients receiving HEC.
Clinical trial identification
Legal entity responsible for the study
Jin-Hyoung Kang, Ph.D, The Catholic University of Korea.
Astellas Pharma Korea. Inc.
J.S. Ahn: Honoraria: Eiasi, Jassen, Menarini, Roche; Advisory role: Boehringer Ingelheim. All other authors have declared no conflicts of interest.