Rolapitant Reduced Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Cisplatin-Based ChemotherapyIn two phase III trials reported in The Lancet Oncology, Rapoport et al found that the addition of rolapitant to serotonin (5-HT3) receptor antagonist and dexamethasone treatment significantly improved complete response rates in prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cisplatin-based chemotherapy.
In the two double-blind phase III trials (HEC-1 and HEC-2), patients from 155 sites (76 in HEC-1 and 79 in HEC-2) in 26 countries (17 in HEC-1 and 14 in HEC-2) were randomly assigned between February 2012 and March 2014 to receive oral rolapitant 180 mg or placebo at 1 to 2 hours before administration of highly emetogenic chemotherapy. All patients received intravenous granisetron 10 μg/kg and oral dexamethasone 20 mg on day 1 and oral dexamethasone 8 mg twice daily on days 2 to 4 for up to six cycles, with a minimum of 14 days.
A total of 526 patients in HEC-1 (264 rolapitant and 262 control patients) and 544 in HEC-2 (271 rolapitant and 273 control patients) received at least one dose of study drug and were included in the modified intention-to-treat population. The primary endpoint was the proportion of patients achieving a complete response, defined as no emesis or use of rescue medication, in the delayed phase (> 24–120 hours after initiation of chemotherapy) in cycle 1.
HEC-1 included greater proportions of women, patients from North America, and cases of ovarian cancer. HEC-2 included greater proportions of patients with lung or stomach cancer.
Significantly greater proportions of patients in the rolapitant groups achieved complete response during the delayed phase in both HEC-1 (73% vs 58%, odds ratio [OR] = 1.9, P = .0006) and HEC-2 (70% vs 62%, OR = 1.4, P = .0426) and in the pooled population (71% vs 60%, OR = 1.6, P = .0001).
The incidence of adverse events was similar in rolapitant and control groups. The most commonly reported treatment-related adverse events during cycle 1 were headache (< 1% vs < 1%), hiccups (< 1% vs < 1%), constipation (< 1% vs < 1%), and dyspepsia (< 1% vs < 1%). The most common grade ≥ 3 adverse events in cycle 1 were neutropenia (3% vs 5% in HEC-1, 6% vs 5% in HEC-2), anemia (< 1% vs < 1% in HEC-1, 3% vs < 1% in HEC-2), and leukopenia (2% vs < 1% in HEC-1, < 1% vs < 1% in HEC-2). No serious adverse events were considered treatment-related.
treatment significantly improved complete response rates in prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cisplatin-based chemotherapy.
were randomly assigned between February 2012 and March 2014 to receive oral rolapitant 180 mg or placebo at 1 to 2 hours before administration of highly emetogenic chemotherapy.
All patients received intravenous granisetron 10?g/kg and oral dexamethasone 20 mg on day 1 and oral dexamethasone 8 mg twice daily on days 2 to 4 for up to six cycles, with a minimum of 14 days.
population (71% vs 60%, OR = 1.6, P = .0001).
and with significant benefit in the pooled population (69% vs 59%, P = .0005).