MADRID — A new neurokinin receptor (NK)-1 antagonist, rolapitant (under development by Tesaro), could soon be available for the prevention of chemotherapy-induced nausea and vomiting (CINV). Rolapitant was significantly better than placebo in a study reported here at the European Society for Medical Oncology Congress 2014.
A complete response was achieved by more of the rolapitant group than of the placebo group for patients in the delayed phase of CINV (72.7% vs 58.4%; P < .001), the acute phase (83.7% vs 73.7%; P = .005), and the overall phase (70.1% vs 56.5%; P = .001).
The manufacturer has submitted the data for approval in the United States.
But the unanswered question is how rolapitant compares with aprepitant(Emend, Merck & Co.), the first and so far only NK-1 antagonist on the market, which is used in conjunction with 5-HT₃ antagonists such as ondansetron. These highly effective drugs "have together dramatically changed the experience of cancer treatment, bringing unprecedented improvements to patients' quality of life," the American Society of Clinical Oncology noted when the agents were recently voted to be among the top 10 clinical cancer advances in the past 50 years. These drugs are all highly active against CINV.
"Nausea and vomiting is the most feared side effect of chemotherapy," said Bernardo L. Rapoport, MD, chief medical oncologist at The Medical Oncology Center of Rosebank in Johannesburg, who presented the rolapitant findings during a press briefing. "It dramatically affects quality of life."
Severe nausea and vomiting is frequently experienced by patients undergoing treatment with cisplatin-based chemotherapy, and can lead to dose reductions and treatment discontinuation.
End Points Met
Rolapitant appears to be different from other agents in this class, in that it does not interact with any other drugs and has a long half-life, Dr. Rapoport noted.
He presented results from a phase 3 multicenter trial that involved 532 patients receiving cisplatin chemotherapy. All received granisetron and dexamethasone. In addition, half received rolapitant and half received placebo.
The primary end point was a complete response (no emesis/no rescue medicines) in the delayed phase (from 24 to 120 hours after chemotherapy). The demographic characteristics of both groups were well balanced, and the median age was 57.3 years (range, 20 to 90).
As well as meeting the primary end point, the secondary end points of a complete response in the acute and overall phases were significantly better with rolapitant. In addition, more patients in the rolapitant group than in the placebo group reported no effect of quality of life (72.8% vs 67.8%; P = .231). Treatment-emergent adverse events were consistent in both groups.
"The majority of adverse events were considered by the investigators to be related to chemotherapy or the underlying cancer, not the drug," said Dr. Rapoport.
Effects were also seen in different geographic regions, he added.
Table. Regional Comparison of Complete Responses
"This agent makes a significant difference in the way people tolerate their chemotherapy," said lead study investigator Martin Chasen, MD, medical director of palliative care at the Ottawa Hospital Cancer Centre in Ontario, Canada.
"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 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 the week after each cycle of cisplatin," Dr. Chasen explained.
"We must treat nausea and vomiting, not just the cancer," ha added, emphasizing that some patients are extremely sensitive to cisplatin effects. He recalled that he had 1 or 2 patients with curable cancers who refused treatment after 1 round of cisplatin. "They preferred to die," he said.
"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," Dr. Chasen reported.
"We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting, and there are other agents that block this for a short time. But rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, not allowing the chemotherapy to induce nausea and vomiting," he explained.
He pointed out that rolapitant might also save money. For example, in Ottawa, after chemotherapy, patients can be visited by a nurse who will administer intravascular hydration and nutrients. "Patients receiving rolapitant may not require this service. They are able to eat and drink as they should," he explained.
During a discussion of the study, Jørn Herrstedt, MD, DMSci, from the Institute of Clinical Research at the University of Southern Denmark in Odense and the Department of Oncology at the Odense University Hospital, agreed with most of the conclusions of the study.
"There was an improvement in quality to life," he noted " but I don't think it's really clinically relevant, as the differences were very small."
The study will probably have an impact on future antiemetic therapy, he added.
The study was sponsored by Tesaro. Some of the study investigators are employees of Tesaro.
European Society for Medical Oncology (ESMO) Congress 201: Abstract LBA47 PR. Presented September 27, 2014.