Phase III study of sustained release granisetron (APF530) compared to palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV)

Abstract

9627 Background: APF530 is a polymeric formulation of granisetron providing sustained drug release over 5 days. Two doses (5 and 10 mg) of subcutaneous APF530 were evaluated in comparison to 0.25 mg intravenous palonosetron. Efficacy was evaluated in acute (0–24 hrs) and delayed (24–120 hrs) CINV among patients receiving moderate (MEC) or highly (HEC) emetogenic chemotherapy. Methods: Randomized, blinded patients (n=1,395) were stratified into MEC or HEC according to Hesketh et al 1999, and assigned to receive either dose of APF530 or palonosetron. Dexamethasone use was standardized based on the emetogenic strata. Patient diaries recorded emetic episodes, nausea and rescue medications over a 5-day period. Primary endpoint was Complete Response (CR), defined as no emetic episodes and no rescue medication. Non-inferiority to palonosetron was declared if the lower bound of the CI for the difference was above -15%. Results: APF530 was well tolerated. Adverse events were consistent with those previously reported for granisetron. For APF530 Tmax was observed about 24 hrs with sustained levels over 120 hrs. For MEC acute phase CR rates of 74.8% (n=214), 76.9% (n=212) and 75.0% (n=208) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 51.4%, 59.0% and 57.7% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. For HEC acute phase CR rates of 77.7% (n=229), 81.3% (n=240) and 80.7% (n=238) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 64.6%, 68.3% and 66.4% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Efficacy was maintained with APF530 over multiple cycles (up to 4). Conclusions: Both doses of APF530 were non-inferior to palonosetron with respect to CR during the acute phase following MEC and HEC. Only the higher dose of APF530 (10 mg granisetron) was non-inferior to palonosetron during the delayed phase of MEC. Both doses of APF530 were comparable to the CR rates of palonosetron during the delayed phase of HEC. [Table: see text]