Rolapitant reduces nausea and vomiting in phase III trial
Rolapitant reduces nausea and vomiting in patients receiving cisplatin-based chemotherapy, according to the results of a phase III trial presented at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain.
“This agent makes a significant difference in the way people tolerate their chemotherapy. Patients experienced no loss in quality of life and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf 1 week after receiving chemotherapy. This is in sharp contrast to many patients on current standard antiemetics [who] are too ill to get out of bed within a week after each cycle of cisplatin," said lead author Martin Chasen, MD, medical director, Palliative Care, Ottawa Hospital Cancer Centre, Canada.
"We must treat nausea and vomiting, not just the cancer," added Chasen, emphasizing that some patients are extremely sensitive to cisplatin effects and recalling that he had one or two patients with curable cancers who refused treatment after one round of cisplatin. "They preferred to die," he said.
The phase III trial investigated rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation. The multicenter trial randomized 532 patients 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to cisplatin-based chemotherapy.
The primary end point was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (more than 24-120 hours) post chemotherapy. Key secondary end points included complete response during the acute (0-24 hours) and overall (0-120 hours) phases.
The trial met its primary end point, with 73% of patients receiving rolapitant achieving complete response in the delayed phase compared with 58% of those receiving placebo (P<.001). Rolapitant also improved the complete response rate compared to placebo in the acute (84% vs 74%, P=.005) and overall (70% vs 57%, P=.001) phases. Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life (73% vs 68%, P=.231).
"Rolapitant demonstrated a significant effect in both the acute and delayed phases. Our primary end point was achieved in the delayed phase, an incredible result. We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting—there are other agents that block this for a short time; rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting," said Chasen.
The investigators tested the agent in patients receiving cisplatin, possibly the strongest inducer of emesis. "Without a doubt this drug can be evaluated in other less emetogenic cancer treatments," said Chasen.
He pointed out that rolapitant may also save costs. For example, in Ottawa, patients can have a visit from a nurse following their chemotherapy who administers intravascular hydration and nutrients. Chasen said: "Patients receiving rolapitant may not require this service. They are able to eat and drink as they should."