Rapoport, B., Chua, D., Poma, A., Arora, S., Wang, Y., & Fein, L.E. (2015). Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). Supportive Care in Cancer, 23, 3281–3288. 

To evaluate the safety and efficacy of four different doses of rolapitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with cisplatin-based, highly emetogenic chemotherapy

Eligible patients were randomized to receive rolapitant at 9, 22.5, 90 or 180 mg or no rolapitant (active control) administered two hours before the first dose of chemotherapy on day 1 of cycle 1 with cisplatin greater than 70 mg/m². Patients also received Zofran^® at 32 mg IV and Decadron^® at 20 mg orally 30 minutes before chemotherapy. Dexamethasone was administered at 8 mg orally twice daily on days 2, 3, and 4.

• N = 454  
• MEDIAN AGE = 55 years (range = 18–86 years)
• MALES: 244 (54%), FEMALES: 210 (46%)
• KEY DISEASE CHARACTERISTICS: No disease characteristics were provided. Patients were receiving highly-emetogenic chemotherapy at 70 mg/m².
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusions included patients who had previously received cisplatin, 5HT3 antagonists, NK1 antagonists, or other drugs that may interfere with the study five days prior to treatment. Patients who had abdominal or pelvis radiation scheduled on day 5 or 6 or were receiving systemic corticosteroids also were excluded.

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: Seventy-five sites in 21 countries

• PHASE OF CARE: Active antitumor treatment

Phase 2, randomized, double-blinded, active-controlled, parallel-group, dose-ranging study

• Patient diary with Visual Analog Scale (VAS) for nausea, emesis episodes, and use of rescue medication
• Functional Living Index-Emesis (FLIE) for quality of life
• Laboratory values, vital signs, electrocardiograms, and physical examinations for safety and tolerability

Rolapitant was well tolerated and was associated with greater complete response rates than the placebo group. Rolapitant at 180 mg achieved a statistically significant improvement compared to the active control group in the acute (87.6% and 66.7%, respectively, p = 0.001) and delayed (63.6% and 48.9%, respectively, p = 0.045) phases. Complete response rates across all phases of CINV were consistently higher for all other rolapitant dose groups compared to the active control group except the 9 mg group in the acute phase. However, this did not achieve statistical significance. Rolapitant also was statistically superior to the active control in other key secondary efficacy variables including less emesis in the acute and delayed phases and less nausea in the acute and delayed phases. Rolapitant at 90 and 180 mg doses significantly improved quality of life compared to the control group. The incidence of serious adverse events was similar in all treatment groups.

All doses of rolapitant were well tolerated and were associated with greater compete response rates than the active control (except 9 mg in the acute phase). Rolapitant at 180 mg demonstrated a clinical statistically significant effect in preventing CINV in the overall, acute, and delayed phases for patients receiving highly emetogenic chemotherapy.

In this study, rolapitant at 180 mg was safe, well tolerated, and effective in controlling CINV in all phases when given in combination with dexamethasone and a 5HT3 receptor antagonist for patients receiving highly emetogenic chemotherapy.