A prospective multicenter, single blinded, randomized phase III trial to compare the efficacy of ramosetron, aprepitant and dexamethasone with ondansetron, aprepitant, and dexamethasone for preventing chemotherapy-induced nausea and vomiting: KCSG PC10-21.

9633 Background: Combination of aprepitant, 5-HT3 receptor antagonist and steroid improve complete response (CR) of chemotherapy induced nausea and vomiting (CINV). But until now, there was no information whether ramosetron is as effective as other 5-HT3receptor antagonists for the combination regimen. Therefore, we compared a ramosetron, aprepitant and dexamethasone (RAD) with ondansetron, aprepitant and dexamethasone (OAD) to establish the non-inferiority of RAD in controlling highly emetogenic chemotherapy induced nausea and vomiting. Methods: A total of 334 patients with malignant disease who were scheduled to receive highly emetogenic chemotherapy were randomized to RAD or OAD. Aprepitant (125 mg day 1; 80 mg day 2, 3) and dexamethasone (12 mg day 1; 8 mg day 2-4) were administered to both group. Intravenous ramosetron (0.3mg day 1) or ondansetron (16mg day1) was given to RAD or OAD, respectively. Patients recorded vomiting and nausea (VAS score) on the diary. The primary end point was CR (no vomiting or retching and no rescue medication) rate in the acute period (chemotherapy day 1). The non-inferiority margin was defined as -15% differences. Results: 299 patients (RAD 143, OAD 156) were eligible for the efficacy analyses of modified intention-to-treat. Median age and sex were 60 (IQR 52 – 66) and 61 (51.5 – 68, p=0.54), 90 Male/66 Female and 114 Male/29 Female (p<0.0001) in RAD and OAD, respectively. There were no significant differences between two groups on the other baseline characteristics. The CR rates of RAD vs OAD were 84.6% vs 77.6% (95% C.I. -0.4 – 14.5%) at acute period, 69.5% vs 62.6% (-2.1 – 16.0%) at delayed period (days 2-5), and 66.7% vs 58.1% (-0.6 – 17.8%) at overall period. Median nausea score at acute period were 4 (IQR 2 – 5) and 3 (2-5, p=0.14) in RAD and OAD, respectively. There were no grade 3 or 4 toxicities. Conclusions: RAD regimen is as effective and tolerable as OAD antiemetic combination for the prevention of CINV in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered as one of the best partners for aprepitant. Clinical trial information: NCT01536691.