Schwartzberg, L.S., Modiano, M.R., Rapoport, B.L., Chasen, M.R., Gridelli, C., Urban, L., . . . Schnadig, I.D. (2015). Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: A randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncology, 16, 1071–1078. 

To assess rolapitant in combination with a serotonin receptor antagonist and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer after the administration of moderately emetogenic chemotherapy (MEC) or regimens containing an anthracycline and cyclophosphamide

Patients received either one oral dose of 180 mg rolapitant or a placebo 1–2 hours before chemotherapy on day 1. All patients received 2 mg granisetron plus 20 mg dexamethasone approximately 30 minutes prior to chemotherapy. Granisetron (2 mg) was also given once daily on days 2 and 3. Additional medications, such as dexamethasone for taxanes, were administered as needed and according to package instructions. Cycles were a minimum of 14 days, and patients received the same regimen (rolapitant or placebo) for up to five subsequent cycles during the study.

• N = 1,333
• AGE RANGE = 22–86 years (rolapitant group), 22–88 years (control group)
• MEDIAN AGE = 58 years (rolapitant group), 56 years (control group)
• MALES: 20% (rolapitant group), 20% (placebo group); FEMALES: 80% (rolapitant group), 80% (placebo group)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: No specific tumor type was recruited; however, the majority of patients had breast cancer or lung cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria required that patients be older than 18 years, have a Karnofsky score of 60 or better, have a life expectancy of four months or greater, and have adequate bone marrow, liver, and kidney functions. Patients with a history of receiving moderately or highly emetogenic chemotherapy or with a contraindication to any of the study drugs were excluded. Also, patients with histories of alcohol misuse, seizure disorders, or psychiatric conditions were excluded.

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Data were collected from 170 study sites in 23 countries located in North, Central, and South Americas; Europe; Asia; and Africa.

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

• Global, multicenter, randomized, double-blind, active-controlled, phase-III trial

Efficacy was measured as a complete response (CR) or no emesis or use of rescue medications as reported in a daily patient journal for up to 120 hours post chemotherapy. Responses were stratified into acute (< 24 hours) and delayed (> 24 hours) phases. Also, the Functional Living Index-Emesis (FLIE) survey was used to measure the effect of nausea or vomiting on daily living. The FLIE uses a seven-point visual analog scale (VAS) on nine questions to assess patients on day 6 of cycle 1. Finally, safety variables (e.g., adverse reactions) were assessed and reported.

The findings showed that a significantly greater proportion of patients receiving rolapitant had CRs in the delayed phase than those who received the active control (95% CI [1.2, 2.0], p = 0.0002). No significance was found in the acute phase between patients receiving rolapitant and the control. Adverse events were similar between groups with the most frequent events being fatigue, constipation, and headache. In cycle 1, grade 3–4 neutropenia was 5% in the rolapitant group and 3% in the active control group.

The findings showed that rolapitant in combination with a 5-HT₃ and dexamethasone was well tolerated and showed superiority over active control for the prevention of CINV during the five-day (0–120 hour) at-risk period after the administration of MEC or drug regimens containing an anthracycline.

• Risk of bias (sample characteristics)
• Sample was disproportionately female.
• The authors referred to both a placebo control and an active control—control condition unclear.

Rolapitant in combination with a 5-HT₃ receptor antagonist and dexamethasone was well tolerated by this sample and demonstrated acceptable extended (0–120 hours) control of CINV associated with MEC regimens and regimens containing an anthracycline and cyclophosphamide.