Copenhagen, Denmark—Rolapitant 180 mg significantly reduced symptoms of chemotherapy-induced nausea and vomiting (CINV) in patients treated with multiple cycles of highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC), according to research presented by Bernardo L. Rapoport, MD, at the 2015 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology Annual Meeting on Supportive Care in Cancer.
Rolapitant is a highly selective, long-acting neurokinin-1 receptor antagonist that has already demonstrated safety and efficacy in treating patients with CINV in cycle 1 of HEC or MEC.
“Its long half-life suggests that a single 180 mg dose will prevent CINV for the entirety of a patient’s 5-day at-risk period,” stated Dr Rapoport, Specialist Physician and Medical Oncologist, The Medical Oncology Centre of Rosebank, Johannesburg, South Africa.
Previously Demonstrated Efficacy
The safety and efficacy of a single oral dose of rolapitant has been previously demonstrated in a large, global, randomized, controlled, double-blind phase 2 study of patients receiving HEC. Its efficacy and safety were also confirmed in 3 large, global, randomized, controlled, double-blind, phase 3 studies of patients receiving HEC or MEC.
Dr Rapoport and colleagues conducted a pooled analysis of 4 similar studies to evaluate the efficacy and safety of rolapitant 180 mg in the prevention of CINV during cycles 2 through 6 of chemotherapy, because patients who experience emesis during initial chemotherapy have an increased risk for CINV during subsequent treatments. “The previous papers looked only at the first cycle of chemotherapy,” the presenter noted.
Study Methods and the Primary End Point
Dr Rapoport reported data from 4 double-blind, active-controlled studies: 1 phase 3 study of patients receiving MEC (N = 1332); 1 phase 2 study of patients receiving HEC (N = 181); and 2 phase 3 studies of patients receiving HEC (N = 1070). Patients were randomized to receive oral rolapitant 180 mg or placebo 1 to 2 hours before chemotherapy. All patients received an active control dose of a 5-hydroxytryptamine receptor antagonist and oral dexamethasone, in addition to rolapitant or placebo.
“As expected, breast cancer was the most common diagnosis for patients receiving MEC chemotherapy,” he explained. “Lung cancer was more common in patients receiving HEC.”
In a daily diary, patients recorded their use of rescue medications and events of emesis that interfered with normal daily life; nausea was self-assessed daily for 5 days. Randomized treatment could be continued in a blinded fashion for up to 5 additional cycles, and was the basis of this analysis, Dr Rapoport said.
The primary end point of the study was the incidence of CINV that interfered with normal daily life following chemotherapy, measured by asking patients 2 questions: “Have you had any episode of vomiting or retching since your chemotherapy started in this cycle?” and “Have you had any nausea since your chemotherapy started in this cycle that interfered with normal daily life?” Incidence was measured on days 6 to 8 of each subsequent cycle of treatment.
Rolapitant Effective Over Multiple Cycles
“Data could be pooled because the studies were similarly designed,” Dr Rapoport explained. “This increased the size of the data set and enabled a robust analysis.”
Effectiveness was maintained over multiple cycles; in each subsequent cycle, a greater proportion of patients on rolapitant versus placebo reported no emesis or nausea disruptive to daily life. “Adverse event rates were high,” he noted. “But there were no differences between the treatment arms, statistically, that could be attributed to this antiemetic regimen.” Treatment-related adverse events were similar in the rolapitant and control groups, with the most common adverse events being constipation and fatigue.
Over multiple cycles of emetogenic chemotherapy, patients taking rolapitant showed significant reductions in symptoms of CINV compared with patients receiving placebo, with no increase in toxicity, the investigators concluded.
