Boccia, R., O'Boyle, E., & Cooper, W. (2016). 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. BMC Cancer, 16, 166-016-2186-4.

To establish the noninferiority of sustained-release granisetron (APF530) for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) compared with palonosetron following highly emetogenic chemotherapy (HEC) and/or MEC chemotherapy in a subpopulation of patients with breast cancer, and to show the superiority of APF530 for the prevention of delayed CINV following HEC with cycle 1 of chemotherapy.

Patients were stratified based on either moderate or high emetogenicity of the chemotherapy. Patients received both IV and subcutaneous injections. Group 1 received 250 mg of APF530 subcutaneously and placebo IV, group 2 received 500 mg of APF530 subcutaneously and placebo IV, and group 3 received placebo subcutaneously and IV palonosetron 0.25 mg. APF530 was given 30 minutes prior to chemotherapy. At the completion of cycle 1, patients who received palonosetron were offered the option to remain in the study. These patients were then rerandomized 1 to 1 to receive doses of 250 versus 500 mg of APF530 subcutaneously during cycles 2–4. Treatment cycles ranged from 7 days–28 days. Rescue medications were permitted with the exception of granisetron, palonosetron, and aprepitant.

• N = 618   
• MEAN AGE = Moderately emetogenic group (53.3 years in APF 250 mg, 54.3 years in APF 500 mg, 55 years in palonestron only); highly emetogenic group (50.3 years in APF 250 mg, 49.8 years in APF 500 mg, 52.6 years in palonosetron only)
• MALES: Less than 2% (n = 5), FEMALES: 98–100% (n = 603)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Breast cancer, does not report staging
• OTHER KEY SAMPLE CHARACTERISTICS: Multiple chemotherapy regimens with less than 70% receiving AC; mostly Caucasian and Asian

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Multiple cancer centers across the United States, India, and Poland

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care 

Prospective, multicenter, randomized, double-blind and double-dummy, parallel-group, phase-III noninferiority trial. Groups were broken into highly emetic and moderately emetic based on Hesketh scores.

• Instruments used to measure CINV are not articulated in this paper.  
• Complete response defined as no emesis and no use of rescue medication.

CR rates with the experimental drug at 250 and 500 mg were not significantly different from those with palonosetron for both HEC and MEC regimens. The effectiveness of APF530 improved in later cycles, although at that point, those patients were no longer receiving palonosetron. No significant differences existed between groups in the samples. No noticeable differences existed between the breast cancer group and the overall population of the study.

Safety: Patients receiving APF530 had more complaints of injection site pain compared to palonosetron. No difference in adverse events existed between the breast cancer group and the overall population of the study.

APF530 is effective in acute and delayed CINV in patients with breast cancer. The side effect profile was similar in all arms of the study and included fatigue, constipation, and headache. The trend to better response is not a reflection of palonosetron, as this agent was not used after cycle 1.

• Measurement/methods not well described
• Unknown instruments to measure CINV
• This is a secondary analysis of a previously published paper from 2014.

Sustained-release granisetron can provide another alternative intervention for CINV prophylaxis; however, it does require subcutaneous injection. Further research is needed to establish the comparative effectiveness of this medication within overall CINV antiemetic regimens.