Palonosetron (PALO) versus granisetron (GRA) in the triplet regimen with dexamethasone (DEX) and aprepitant (APR) for preventing chemotherapy-induced nausea and vomiting (CINV) in patients (pts) receiving highly emetogenic chemotherapy (HEC) with cisplatin (CDDP): A randomized, double-blind, phase III trial.

Abstract

9621 Background: Standard antiemetic care for preventing CINV due to HEC is a combination of 5-HT3 receptor antagonist (RA), DEX, and APR. This study compared the efficacy of two 5-HT3drugs, PALO and GRA, in the triplet regimen. Methods: Pts with a malignant solid tumor who were receiving HEC containing 50 mg/m2or more CDDP were enrolled. They were randomly assigned to either Arm A (PALO 0.75 mg, i.v.) or Arm B (GRA 1 mg, i.v.), 30 min before chemotherapy on day 1, both arms with DEX (9.9 mg on day 1 and 6.6 mg on day 2-4, i.v.) and APR (125 mg on day 1 and 80 mg on day 2–3, p.o.). Primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medications) at the overall (0-120 hours) phase. Secondary endpoints included CR at the acute (0-24 h) and delayed (24-120 h) phases, and total control (TC; no emetic episodes, no rescue medications, and no nausea) at the overall, acute, and delayed phases. The planned sample size of 840 provided 90% power to detect a 10% improvement in the CR at 0-120 h with two-sided alpha of 0.05. Primary analysis was conducted with exact Cochran-Mantel-Haenszel (CMH) test. Results: Between July 2011 and June 2012, 842 pts were enrolled and 827 were evaluable. The median CDDP dose was 76.1 mg/m2 in Arm A and 75.7 mg/m2in Arm B. Baseline factors were well-balanced. Efficacy results are summarized in the Table. Conclusions: The present study did not meet its primary endpoint. However, it has shown that the clinical utility of PALO exceeds that of GRA. PALO is a more preferable 5-HT3RA in the triplet regimen than GRA in the prevention of CINV due to HEC. Clinical trial information: 000004863. [Table: see text]