Palonosetron (PALO) versus granisetron (GRAN), both combined with dexamethasone (DEX) in preventing chemotherapy-induced nausea and vomiting (CINV) associated with cisplatin- or anthracycline plus cyclophosphamide-based regimens: Results of a phase III trial in Japanese patients

Abstract

20749 Background: PALO is a pharmacologically distinct 5-HT3 receptor antagonist with unique molecular interactions with the 5-HT3 receptor compared with GRAN. Methods: This multicenter, randomized, double-blind, stratified, phase III trial assessed the efficacy/safety of a single IV dose of PALO 0.75 mg vs IV GRAN 40 μg/kg (∼3mg) administered 30 min prior to cisplatin ≥50 mg/m2 (CDDP) or anthracycline + cyclophosphamide (AC/EC). Selection of the PALO dose was based on two Phase II dose-ranging trials and the dose of GRAN is the approved dose in Japan. DEX 16 mg IV was administered before chemotherapy (CT) on day 1, and 8 mg IV (CDDP) or 4 mg orally (AC/EC) on days 2–3. Stratification factors were gender, age and CT. The study was designed to demonstrate non-inferiority on day 1 and superiority on days 2–5 of PALO vs GRAN, combined with DEX. The primary endpoint was the complete response rate (CR = no emesis, no rescue medication). Adverse events (AEs) were assessed according to NCI-Common Toxicity Criteria. Results: A total of 1,114 pts (58% women; mean age 58) were evaluated; 57% received CDDP, 43% AC/EC. The CR rate for PALO was equivalent to GRAN in acute phase and significantly greater than GRAN in delayed phase (Table). Overall CR (0–120 h) was also greater for PALO (51.5%) vs GRAN (40.4%). Time to treatment failure was significantly longer for PALO with separation in the curves at 16 hrs after CT on day 1 (Hazard Ratio: 1.30, 95% CI: 1.106-1.526). The incidence, pattern or intensity of AEs did not differ between PALO and GRAN. Conclusions: A single dose of PALO resulted in a comparable prevention of CINV to GRAN at the end of day 1, and demonstrated superior long-lasting CINV prevention in the delayed phase in patients receiving highly emetogenic CT. CR rates Period CR (%) PALO vs GRAN p-value PALO 0.75 mg (N=555) GRAN 40 μg/kg (N=559) PALO minus GRAN Acute (0–24 hrs) § 77.5 75.2 2.29 [-2.70, 7.27]† Not done Delayed (24–120 hrs) 56.8 44.5 12.3 < 0.001* § : mean of minimum squared values adjusted with stratified factors (CT, gender and age) † : lower limit >-10% indicates non-inferiority of PALO against GRAN * : Cochran-Mantel-Haenszel test stratified with CT, gender and age No significant financial relationships to disclose.