Schnadig, I.D., Agajanian, R., Dakhil, C., Gabrail, N.Y., Smith, R.E., Taylor, C., . . . Vacirca, J.L. (2016). APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy. Future Oncology, 12, 1469–1481 

To compare the efficacy and safety of granisetron injection extended-release (APF530) versus ondansetron for delayed chemotherapy-induced nausea and vomiting (CINV) after highly emetogenic chemotherapy, following a guideline-recommended three-drug regimen

Patients receiving highly emetogenic chemotherapy were randomized into either the APF530 or ondansetron arm for the study. Patients in the APF530 arm received APF530 500 mg subcutaneously and saline placebo in place of ondansetron. Patients in the ondansetron arm received ondansetron 0.15 mg/kg intravenously and a saline placebo subcutaneously in place of APF530 on day 1. All patients also received fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1; dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3–4. A topical anesthetic was applied to the injection site before APF530 or its placebo were administered. On day 1, all study medications were administered 30 minutes before the start of chemotherapy.

• N = 902   
• MEAN AGE = 55.7 years and 55.6 years for the APF530 and placebo arms, respectively
• MALES: 20.4% and 17.5% of patients enrolled in the APF530 and placebo arms, respectively; FEMALES: 79.6% and 82.5% of patients enrolled in the APF530 and placebo arms, respectively
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: No specific tumor types were recruited.
• OTHER KEY SAMPLE CHARACTERISTICS: Men and women aged 18–80 years receiving the first cycle of a single-day highly emetogenic chemotherapy for a histologically or cytologically confirmed malignancy

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Seventy-seven medical centers across the United States

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

• Prospective, randomized, double-blind, double-dummy, parallel-group, multicenter, phase-III trial

Patients were monitored during four clinic visits:

• screening: day –21 to –1
• baseline/day 1 
• day 6 
• final safety follow up on the day of the patient’s next chemotherapy administration

Patients completed symptom diaries during days 1–6 to self-report nausea, vomiting, retching, and rescue medication usage.

A higher percentage of patients receiving APF530 had delayed-phase complete response when compared to patients receiving ondansetron. The absolute treatment difference was 8% (95% CI [1.7, 14.4], p = 0.014). Delayed-phase CR rates for the cisplatinum arm were 65.3% with the APF530 regimen and 54.7% with the ondansetron regimen. The absolute treatment difference here was 10.6% (95% CI [–1.4, 22.7]). For the non-cisplatinum arm, the delayed-phase CR rates were 64.4% for APF530 and 57.4% for ondansetron regimens. This absolute treatment difference was 7% (95% CI [–0.9, 12.1], unadjusted p = 0.092).

APF530 provided superior control of delayed-phase CINV after highly emetogenic chemotherapy when compared with standard three-drug regimens.

• Short follow-up time

APF530 was found to be a well-tolerated  extended-release granisetron formula with clinical benefit for the control of CINV after highly emetogenic chemotherapy.