Rapoport, B., Schwartzberg, L., Chasen, M., Powers, D., Arora, S., Navari, R., & Schnadig, I. (2016). Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy. European Journal of Cancer, 57, 23–30. 

To explore the efficacy and safety of rolapitant in preventing chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC)

Patients were stratified by gender to receive either 180 mg oral rolapitant or placebo approximately 1–2 hours before receiving either MEC or HEC. All patients received a 5-HT₃ antiemetic and dexamethasone. Patients receiving MEC were given 2 mg oral granisetron on days 1–3 and 20 mg dexamethasone on day 1. Patients receiving HEC (e.g., cisplatin-based chemotherapy) were given 10 mc/kg granisetron intravenously and oral 20 mg dexamethasone on day 1 and 8 mg twice daily on days 2–4. Patients receiving taxanes were given dexamethasone per the package insert.

• N = 1,998   
• AGE RANGE = 18–90 years
• MEAN AGE = 57 years
• MALES: 38.4% (intervention arm), 36.9% (control arm); FEMALES: 61.6% (intervention arm), 63.1% (control arm)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients were not recruited or stratified by specific tumor type. More than half of the patients (67%) had breast cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria required that patients be aged 18 or older, have a Karnofsky score of 60 or better, have a life expectancy of four months or longer, and have adequate bone marrow, liver, and kidney functions. Patients in the MEC group were required to be naïve to MEC or HEC and scheduled to receive their first course of IV cyclophosphamide (< 1500 mg/m²), doxorubicin, epirubicin, carboplatin, idarubicin, ifosfamide, irinotecan, daunorubicin, and/or IV cytarabine (> 1 g/m²). At least 50% of the patients were to receive an AC-based (doxorubicin and cyclophosphamide) regimen. Patients in the HEC arm were required to be naïve to cisplatin and scheduled to receive their first course of cisplatin-based chemotherapy.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Multinational—North, Central, and South America; Europe; Asia; and Africa

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

• Global, randomized, double-blind, placebo-controlled studies

Patients were given a diary to record all episodes of nausea, vomiting, and use of rescue drugs for five days post chemotherapy administration during cycle 1. For subsequent cycles, patients were asked two CINV assessment questions on days 6–8: (a) Have you had any episodes of vomiting or retching since your chemotherapy started in this cycle? and (b) Have you had any nausea since your chemotherapy started in this cycle that interfered with normal daily life? Assessments of safety variables, such as adverse events, vital signs, physical and neurological exams, electrocardiograms, and clinical lab values, were assessed during all cycles.

Compared to the control group, more patients receiving rolapitant reported no emesis or interfering nausea in cycles 2 (p = 0.006), 3 (p < 0.001), 4 (p = 0.001), and 5 (p = 0.021) when compared to the control group. Time to first emesis was significantly longer for the rolapitant group in cycles 1–6 (p < 0.001). The incidence of treatment-related adverse events were only slightly lower in the rolapitant (5.5%) than the control group (6.8%) during cycles 2–6.

Oral rolapitant was effective in protecting against CINV over multiple cycles of MEC and HEC. Rolapitant was well tolerated and demonstrated no increased frequency of adverse effects and no cumulative toxicity over multiple cycles.

Women were disproportionately high in the MEC study largely because of the high number of patients with breast cancer receiving AC chemotherapy.

The findings support the possible benefits of adding rolapitant to the therapy of patients receiving MEC and HEC.