Analysis of phase III clinical studies for palonosetron, ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV).

9091 Background: Controlling CINV is integral to treatment success in cancer patients. Palonosetron HCl (PALO) is a potent 5-HT3 receptor antagonist with a longer t½ & a distinctly different receptor binding profile compared to 1st generation 5-HT3 receptor antagonists (1st 5HT3-RA). Methods: We conducted an analysis of 4 multicenter, phase III, randomized, double-blind, parallel & active comparator studies to assess the comparative safety & effectiveness of single IV doses of PALO 0.25mg / 0.75mg to 1st 5HT3-RAs ondansetron 32mg, dolasetron 100mg, & granisetron 3mg in the prevention of CINV. Results: Pooled patient-level data was used from all 4 phase III clinical studies in CINV. The primary efficacy assessment was a comparison of complete response (CR), defined as no emetic episode & no rescue medication for 0-24hrs (acute), >24-120hrs (delayed), & 0-120hrs (overall) using a logistic regression model with terms for PALO 0.25, PALO 0.75, HEC, MEC, Japanese study, Breast Cancer, Lung Cancer, & interaction terms for Breast Cancer & Lung Cancer with PALO. A comparative descriptive safety assessment was also conducted. A total of 2969 patients were included in the analysis-PALO 0.25mg, n=609; PALO 0.75mg, n=1182; & 1st 5HT3-RA, n=1178. Significantly higher CR rates were demonstrated for all PALO doses vs. 1st 5HT3-RA during the acute (0-24hr) phase, OR=0.89; p<0.01; delayed (>24-120hr) phase, OR=0.81, p<0.0001; & overall (0-120hr) phase, OR=0.81, p<0.0001. The adverse event (AE) profile of all doses of PALO was similar to 1st 5HT3-RA in all trials, with up to 96.8% of patients reporting an AE. The incidence of treatment-related AEs was also similar across trials; PALO 0.25mg, up to 20.5%; PALO 0.75mg, up to 28.8%; & 1st 5HT3-RA, up to 32.2%. The most notable TEAEs were constipation (PALO 0.25mg, up to 4.5%; PALO 0.75mg, up to 16.6%; 1st 5HT3-RA, up to 15.4%.) & headache (PALO 0.25mg, up to 9.7%; PALO 0.75mg, up to 12.4%; 1st Gen 5HT3-RA, up to 11.0%). Conclusions: This analysis demonstrated a similar safety profile & significantly improved CINV prophylaxis in the acute, delayed, and overall phase for palonosetron compared to 1st 5HT3-RA.