Abstract
BackgroundAPF530 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.MethodsPatients 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.ResultsAmong 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.ConclusionsAPF530 effectively prevented acute and delayed CINV over 4 chemotherapy cycles in breast cancer patients receiving MEC or HEC.Trial registrationClinicaltrials.gov identifier: NCT00343460 (June 22, 2006).
Highlights
APF530 provides controlled, sustained-release granisetron for preventing acute (0–24 h) and delayed (24–120 h) chemotherapy-induced nausea and vomiting (CINV)
Chemotherapeutic agents were first classified by Hesketh according to their emetogenic potential in the absence of antiemetic prophylaxis, with the risk of CINV being 31–90 % in patients receiving moderately emetogenic chemotherapy (MEC) and > 90 % in patients receiving highly emetogenic chemotherapy (HEC) [5, 6]
Current antiemetic guidelines are similar with respect to the prevention of CINV after HEC, recommending a combination of a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, dexamethasone, and a neurokinin 1 (NK-1) antagonist
Summary
Details of the study design and methodology have been presented elsewhere [19]; a brief overview is presented here. Patients were stratified according to the emetogenicity of their scheduled chemotherapy regimen (MEC or HEC). Patients Eligible patients included adult (≥ 18 years old) men or women with histologically or cytologically confirmed malignancy who were scheduled to receive single-day MEC (Hesketh score 3 or 4) or HEC (Hesketh score 5) regimens according to -applicable Hesketh emetogenicity criteria [5, 20]. Treatment regimens Patients were stratified according to the emetogenicity of their chemotherapy regimen (MEC or HEC) and randomized 1:1:1 to receive APF530 250 mg SC (granisetron 5 mg) plus placebo IV; APF530 500 mg SC (granisetron 10 mg) plus placebo IV; or palonosetron 0.25 mg IV plus placebo SC (Fig. 1). Statistical analysis Efficacy analyses were performed separately for the MEC and HEC strata within the breast cancer subpopulation of the modified intent-to-treat (mITT) group, comprising all randomized patients who received study drug and had postbaseline efficacy data. Comparisons between the breast cancer population and overall population were exploratory in nature and not conducted to evaluate inferiority
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