Randomized phase III trial of APF530 versus palonosetron in the prevention of chemotherapy-induced nausea and vomiting in a subset of patients with breast cancer receiving moderately or highly emetogenic chemotherapy

Ralph Boccia, Erin O'Boyle, William Cooper, Ralph Boccia, Erin O'Boyle, William Cooper

Abstract

Background: APF530 provides controlled, sustained-release granisetron for preventing acute (0-24 h) and delayed (24-120 h) chemotherapy-induced nausea and vomiting (CINV). In a phase III trial, APF530 was noninferior to palonosetron in preventing acute CINV following single-dose moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV in MEC (MEC and HEC defined by Hesketh criteria). This exploratory subanalysis was conducted in the breast cancer subpopulation.

Methods: Patients were randomized to subcutaneous APF530 250 or 500 mg (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg during cycle 1. Palonosetron patients were randomized to APF530 for cycles 2 to 4. The primary efficacy end point was complete response (CR, no emesis or rescue medication) in cycle 1.

Results: Among breast cancer patients (n = 423 MEC, n = 185 HEC), > 70 % received anthracycline-containing regimens in each emetogenicity subgroup. There were no significant between-group differences in CRs in cycle 1 for acute (APF530 250 mg: MEC 71 %, HEC 77 %; 500 mg: MEC 73 %, HEC 73 %; palonosetron: MEC 68 %, HEC 66 %) and delayed (APF530 250 mg: MEC 46 %, HEC 58 %; 500 mg: MEC 48 %, HEC 63 %; palonosetron: MEC 52 %, HEC 52 %) CINV. There were no significant differences in within-cycle CRs between APF530 doses for acute and delayed CINV in MEC or HEC in cycles 2 to 4; CRs trended higher in later cycles, with no notable differences in adverse events between breast cancer and overall populations.

Conclusions: APF530 effectively prevented acute and delayed CINV over 4 chemotherapy cycles in breast cancer patients receiving MEC or HEC.

Trial registration: Clinicaltrials.gov identifier: NCT00343460 (June 22, 2006).

Figures

Fig. 1
Fig. 1
Study design. aPatient numbers refer to the breast cancer modified intent-to-treat population. IV, intravenously; SC, subcutaneously
Fig. 2
Fig. 2
Patient disposition of the overall population in the randomized, double-blind, noninferiority phase III trial (chemotherapy cycle 1). aAccording to Hesketh criteria [5]. bSafety population. (From Raftopoulos et al. [19], with permission)
Fig. 3
Fig. 3
Complete response rates to APF530 250 and 500 mg SC and palonosetron 0.25 mg IV. Graphs show complete response rates in breast cancer patients receiving 4 cycles of (a) moderately emetogenic chemotherapy or (b) highly emetogenic chemotherapy regimens
Fig. 4
Fig. 4
Comparison of complete response rates in cycle 1. Graphs show comparisons between patients with breast cancer and overall study population with (a) moderately emetogenic chemotherapy and (b) highly emetogenic chemotherapy regimens. IV intravenously; SC subcutaneously

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