Rapoport, B.L., Chasen, M.R., Gridelli, C., Urban, L., Modiano, M.R., Schnadig, I.D., . . . Navari, R.M. (2015). Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: Two randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncology, 16, 1079–1089. 

DOI Link

Study Purpose

To assess the safety and efficacy of 180 mg rolapitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who receive moderately or highly emetogenic chemotherapy (HEC)

Intervention Characteristics/Basic Study Process

Patients who had a KPS of 60 or higher, were expected to live at least four months, and had adequate bone marrow and liver and kidney function were randomly assigned to receive 180 mg of rolapitant versus placebo, which looked exactly like the rolapitant.

Sample Characteristics

  • N = 1,087 (from two identically designed global studies)
  • MEAN AGE = 58.8 years
  • MALES: 63%, FEMALES: 37%
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS Most common primary tumor was lung (44%), followed by head and neck (18%)
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients who had a KPS of 60 or higher, were expected to live at least four months, and had adequate bone marrow and liver and kidney function

Setting

  • SITE: Multi-site   
  • SETTING TYPE: Multiple settings    
  • LOCATION: International study

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Study Design

This article describes two randomized, double-blind, active-control studies.

Measurement Instruments/Methods

The primary end point was the proportion of patients achieving a complete response (no emesis or use of rescue drugs). Secondary end points included the proportion of patients achieving complete response in the acute and overall phases (0–120 hours). Efficacy also included the delayed phase. The primary assessment was self-report in daily diaries. In addition, the Functional Living Index-Emesis (FLI-E) questionnaire was used to measure the effect of CINV on daily life. The FLI-E questionnaire was completed on day 6. Safety variables included adverse events, physical and neurological examinations, vital signs, and clinical laboratory values.

Results

In both studies (and in the pooled results), treatment with rolapitant resulted in a significantly increased number of patients experiencing a complete response in the delayed phase. The pooled studies found significant difference in the acute phase (first 24 hours). In the overall phase, complete response was significantly more frequent in the first study and in the results of the pooled studies. No significant differences were observed between study groups with respect to daily living as measured by the FLI-E questionnaire.

Conclusions

Oral rolapitant taken once daily before chemotherapy in combination with a 5-HT3 receptor antagonist and dexamethasone is superior to 5-HT3 receptor antagonist and corticosteroid alone.

Limitations

The study participants were enrolled prior to recommendations for the addition of an NK1 receptor antagonist to standard care and the use of dexamethasone to HEC.

Nursing Implications

As now accepted, the addition of an NK1 receptor antagonist reduces CINV experienced by patients receiving HEC. Patient education regarding adherence to medications and correct timing can help them prevent what is often the most worrisome side effect.